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Being one of the most successful surgeries in the history of medicine, the indications for total hip arthroplasty have widened and are increasingly being offered to younger and fitter patients. This has also led to high expectations for longevity and outcomes. Acetabular cup position has a significant impact on the results of hip arthroplasty as it affects dislocation, abductor muscle strength, gait, limb lengths, impingement, noise generation, range of motion (ROM), wear, loosening, and cup failure. The variables in cup position are depth, height, and angular position (anteversion and inclination). The implications of change in depth of center of rotation (COR) are medialized versus anatomical positioning. As opposed to traditional medialization with beneficial effects on joint reaction force, the advantages of an anatomical position are increasingly recognized. The maintained acetabular offset offers advantages in terms of ROM, impingement, cortical rim press fit, and maintaining medial bone stock. The height of COR influences muscle activity and limb lengths and available bone stock for cup support. On the other hand, ideal angular position remains a matter of much debate and reliably achieving a target angular position remains elusive. This is not helped by variations in the way we describe angular position, with operative, radiologic, or anatomic definitions being used variably to describe anteversion and inclination. Furthermore, pelvic tilt plays a major role in functional positions of the acetabulum. In addition, commonly used techniques of positioning often do not inform us of the real orientation of the pelvis on operating table, with possibility of significant adduction, flexion, and external rotation of the pelvis being possibilities. This review article brings together the evidence on cup positioning and aims to provide a systematic and pragmatic approach in achieving the best position in individual cases.

Biomechanics of the hip joint describes how the complex combination of osseous, ligamentous, and muscular structures transfers the weight of the body from the axial skeleton into the appendicular skeleton of the lower limbs. Throughout history, several biomechanical studies based on theoretical mathematics, in vitro, in vivo as well as in silico models have been successfully performed. The insights gained from these studies have improved our understanding of the development of mechanical hip pathologies such as osteoarthritis, hip fractures, and developmental dysplasia of the hip. The main treatment of end-stage degeneration of the hip is total hip arthroplasty (THA). The increasing number of patients undergoing this surgical procedure, as well as their demand for more than just pain relief and leading an active lifestyle, has challenged surgeons and implant manufacturers to deliver higher function as well as longevity with the prosthesis. The science of biomechanics has played and will continue to play a crucial and integral role in achieving these goals. The aim of this article, therefore, is to present to the readers the key concepts in biomechanics of the hip and their application to THA.

International audience; Osteoarthritis is a degenerative pathology leading to degradation of the extracellular matrix (ECM). Similar effects can be visualized when applying mechanical or biochemical constraints on cartilaginous tissue. Here, we characterized modification of the ECM appearing under mechanical compression and/or biochemical action (hypoxia environment, nitric oxide and collagenase action). In recent decades, multiphoton microscopy has proved its interest for observing living, thick and opaque biological tissues. Thus, the main components of the cartilaginous ECM can be observed without fluorescent labeling. In particular, the collagen network emits strong second harmonic generation (SHG) signal which could be collected at half of the excitation wavelength. Combining autofluorescence and SHG signal detection enables to obtain complementary structural information. Here, we proved that multiphoton microscopy represents an appropriate tool for ex vitro cartilage imaging. First, we showed that SHG signal specifically comes from collagen (collagenase digestion). Further, we verified that the use of an appropriate band-pass filter enables to reject the autofluorescence from the ECM. Once this specificity was shown, we followed modification of the cartilage ECM submitted to mechanical or biochemical constraints (compression, enzymatic digestion). By performing textural analysis of SHG images (Haralick's method), we showed the restructuration of the collagen network according to constraints.

International audience; The described experiment investigated whether adaptation to successive Achilles tendon vibration depends on the postural challenge. In phase 1, thirty-six participants were divided into three groups, each with a different postural challenge. After being blindfolded, participants received 15 trials of Achilles tendon vibration (10 s-90 Hz) while standing upright in either a free-standing condition (FS group), a light finger touch condition (LFT group), or a restrained-standing condition (RS group) in which a dorsal stand prevented body displacement. In phase 2, all participants were freely standing and received 15 additional trials of vibration. Antero-posterior trunk tilt was measured at the level of the trunk (C7). Although there were limited postural readjustments in LFT, adaptation was observed in phase 1 in both FS and LFT groups. In phase 2, the evoked postural displacement was greater in the RS group than in the other two groups. We concluded that although the absence of any postural challenge concomitant to the sensory stimulation prevented adaptation to occur, a minimal challenge was sufficient.

International audience; Cortical bone is more and more considered as a porous medium and this induces the necessity of the determination of the physical properties associated with such a concept: the porosity and the permeability. If porosity does not present a major problem, at least for the order of magnitude, there is a difficulty for the permeability. According to experimental sources, values vary between 10(- 13) and 10(- 23) m(2): it seems obvious that the same entities have not been measured. This article proposes a new vision of the permeability based on a concept of multi-scale medium corresponding to the scales already introduced in the SiNuPrOs model which has been developed for cortical bone. According to this model, several architectural levels are proposed and a mathematical development based on the homogenisation theory, which can be applied to each of these levels, allows a numerical computation of the permeability tensor coefficients. A comparative analysis of our simulations and some experimental results (already published) shows a good accordance with the literature.

Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregate's shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses (“fluctuation-induced flow”). If not, changing the aggregate's shape requires a sufficiently large applied stress (“stress-induced flow”). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress τ*, the aggregate as a whole flows with an apparent viscosity η*, and at higher stress it is a shear-thinning fluid. An increasing cell–cell tension results in a higher η* (and thus a slower stress relaxation time t c ). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find t c of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration.

International audience; We determined the flexural (bending) rigidities of actin and cofilactin filaments from a cosine correlation function analysis of their thermally driven, two-dimensional fluctuations in shape. The persistence length of actin filaments is 9.8 microm, corresponding to a flexural rigidity of 0.040 pN microm(2). Cofilin binding lowers the persistence length approximately 5-fold to a value of 2.2 microm and the filament flexural rigidity to 0.0091 pN microm(2). That cofilin-decorated filaments are more flexible than native filaments despite an increased mass indicates that cofilin binding weakens and redistributes stabilizing subunit interactions of filaments. We favor a mechanism in which the increased flexibility of cofilin-decorated filaments results from the linked dissociation of filament-stabilizing ions and reorganization of actin subdomain 2 and as a consequence promotes severing due to a mechanical asymmetry. Knowledge of the effects of cofilin on actin filament bending mechanics, together with our previous analysis of torsional stiffness, provide a quantitative measure of the mechanical changes in actin filaments associated with cofilin binding, and suggest that the overall mechanical and force-producing properties of cells can be modulated by cofilin activity.

International audience; In occupational situations, accidents referred to as accidents on the level (AoLs) occur most of the time when locomotion control fails. This control is determined by the interactions between the operator and the environment, the task and the used tools. Hence, AoLs prevention requires developing ways to optimise these interactions. More fundamentally, AoLs prevention requires understanding locomotion control in situations where this control is at sake, that is in situations involving one or more AoLs factors. The purpose of this article is to propose a comprehensive model for the control of locomotion in occupational environments. This model featuring the operator, the task and the working space should be an appropriate tool to understand AoLs in the scope of their prevention. Firstly, we describe what occupational AoLs are. In a second part, we present a review of the theoretical and experimental knowledge related to the locomotion system through the various means developed by the Central Nervous System to cope with perturbations of the environment and/or particular constraints from the task. Finally, we propose a simplified systemic model presenting the various levels of control (sensory-motor to cognitive levels) describing locomotion in occupational situations, and we suggest experiments likely to produce the appropriate data to construct the final comprehensive model.; Les accidents du travail répertoriés comme étant des accidents de plain-pied sont dans la plupart des cas occasionnés par une perturbation de la locomotion. Or le contrôle de la locomotion est déterminé par les interactions entre l'opérateur et son environnement, sa tâche ainsi que les outils utilisés. En conséquence, la prévention des accidents de plain-pied passe par l'optimisation de ces interactions. D'un point de vue fondamental, elle nécessite la compréhension du contrôle de la locomotion dans des situations où ce contrôle est compromis, c'est à dire des situations comportant un voire plusieurs facteurs d'accident de plain-pied. Cet article propose un modèle de connaissance du contrôle de la locomotion en situations de travail. Ce modèle qui intègre l'opérateur, sa tâche ainsi que l'espace de travail est un outil destiné à comprendre ces accidents pour mieux les prévenir. Après avoir décrit les accidents de plain-pied, les connaissances théoriques et expérimentales concernant le système locomoteur sont synthétisées, en particulier les moyens développés par le système nerveux central pour faire face aux perturbations induites par l'environnement et/ou par la tâche réalisée. Un modèle systémique simplifié présentant les différents niveaux de contrôle (sensori-moteur et cognitif) de la locomotion en situation de travail est alors proposé suggérant des expérimentations susceptibles de progresser dans la validation du modèle.

Synthetic bone substitutes, such as calcium phosphate ceramics, give good results in clinical applications. In order to adapt to surgical sites, bioceramics come in the form of blocks or granules, and are either dense or porous. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial with the biochemical properties of each component. Critical-sized defects in the femoral condyle of rabbits were filled with TricOs/fibrin glue/bone marrow hybrid/composite material. The TricOs granules (1–2 mm) were composed of hydroxyapatite and beta tricalcium phosphate (60/40 in weight). The fibrin glue was composed of fibrinogen, thrombin and other biological factors and mixed with MBCP granules either simultaneously or sequentially. Bone marrow was also added to the MBCP/fibrin composite prior to filling the defects. After 3, 6, 12, and 24 weeks of implantation, the newly-formed bone was analysed with histology, histomorphometry and mechanical tests. The newly-formed bone had grown centripetally. Simultaneous application of fibrin glue showed better results for mechanical properties than sequential application after 6 weeks. Around 40% of bone had formed after 24 weeks in the three groups. Although the addition of bone marrow did not improve bone formation, the MBCP/fibrin material could be used in clinical bone filling applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

International audience; The nervous system controls the behavior of complex kinematically redundant biomechanical systems. How it computes appropriate commands to generate movements is unknown. Here we propose a model based on the assumption that the nervous system: 1) processes static (e.g., gravitational) and dynamic (e.g., inertial) forces separately; 2) calculates appropriate dynamic controls to master the dynamic forces and progress toward the goal according to principles of optimal feedback control; 3) uses the size of the dynamic commands (effort) as an optimality criterion; and 4) can specify movement duration from a given level of effort. The model was used to control kinematic chains with 2, 4, and 7 degrees of freedom [planar shoulder/elbow, three-dimensional (3D) shoulder/elbow, 3D shoulder/elbow/wrist] actuated by pairs of antagonist muscles. The muscles were modeled as second-order nonlinear filters and received the dynamics commands as inputs. Simulations showed that the model can quantitatively reproduce characteristic features of pointing and grasping movements in 3D space, i.e., trajectory, velocity profile, and final posture. Furthermore, it accounted for amplitude/duration scaling and kinematic invariance for distance and load. These results suggest that motor control could be explained in terms of a limited set of computational principles.

It is obvious, at least qualitatively, that small animals move their locomotory apparatus faster than large animals: small insects move their wings invisibly fast, while large birds flap their wings slowly. However, quantitative observations have been difficult to obtain from free-ranging swimming animals. We surveyed the swimming behaviour of animals ranging from 0.5 kg seabirds to 30 000 kg sperm whales using animal-borne accelerometers. Dominant stroke cycle frequencies of swimming specialist seabirds and marine mammals were proportional tomass−0.29(R2=0.99,n=17 groups), while propulsive swimming speeds of 1–2 m s−1were independent of body size. This scaling relationship, obtained from breath-hold divers expected to swim optimally to conserve oxygen, does not agree with recent theoretical predictions for optimal swimming. Seabirds that use their wings for both swimming and flying stroked at a lower frequency than other swimming specialists of the same size, suggesting a morphological trade-off with wing size and stroke frequency representing a compromise. In contrast, foot-propelled diving birds such as shags had similar stroke frequencies as other swimming specialists. These results suggest that muscle characteristics may constrain swimming during cruising travel, with convergence among diving specialists in the proportions and contraction rates of propulsive muscles.

10 pages; Sessile organisms often exhibit morphological changes in response to permanent exposure to mechanical stimulation (wind or water movements). The adaptive value of these morphological changes (hydrodynamic performance and consequences on fitness) has not been studied extensively, particularly for higher plants submitted to flow stress. The aim was to determine the adaptive value of morphological patterns observed within two higher aquatic plant species, Berula erecta and Mentha aquatica, growing along a natural flow stress gradient. The hydrodynamic ability of each ramet was investigated through quantitative variables (drag coefficient and E-value). Fitness-related traits based on vegetative growth and clonal multiplication were assessed for each individual. For both species, the drag coefficient and the E-value were explained only to a limited extent by the morphological traits used. B. erecta exhibited a reduction in size and low overall plant drag at higher flow velocities, despite high drag values relative to leaf area, due to a low flexibility. The plants maintained their fitness, at least in part, through biomass reallocation: one tall ramet at low velocity, but shorter individuals with many interconnected stolons when flow velocity increased. For M. aquatica, morphological differences along the velocity gradient did not lead to greater hydrodynamic performance. Plant size increased with increasing velocities, suggesting the indirect effects of current favouring growth in high velocities. The fitness-related traits did not demonstrate lower plant fitness for high velocities. Different developmental constraints linked to plant morphology and trade-offs between major plant functions probably lead to different plant responses to flow stress.

Two experiments investigated manual asymmetries in the control of rapid reaching movements according to the movement parameters to be controlled. Single- and double-step reaching movements were performed by right-handed subjects with both hands. Pro and retroactive processes involved in rapid movement control were investigated. Manual performances and kinematic properties of hand movements showed that various forms of hemispheric specialization were involved in sensori-motor information processing. It was shown that the effects of hemispheric specialization were specific to the task constraints, that is, to the various operations involved in movement control.

The aim of the present study was twofold: first, to investigate the effects of spatial precues on the execution of rapid aiming in children aged 7, 9, and 11 and second, to provide a kinematic support to the investigation of the role of precues in aiming tasks performed under temporal constraints. Four precuing conditions were used, where participants received: (a) no precue of any type, (b) advance information on direction, (c) advance information on amplitude, and (d) complete information on the forthcoming movement. Our results showed that precuing the spatial dimensions of movement shortens reaction times, that such shortening is a function of the number of precued parameters, and that spatial precues modify the kinematics of the children's rapid aiming movements. Peak velocity increased with direction and/or amplitude, suggesting that precues play a significant role in motor preparation. Moreover, the accuracy results indicate that direction precuing induces a proactive directional regulation. Finally, direction and amplitude appear to be independently specified in children.

International audience; In most bacteria, the timing and synchrony of initiation of chromosomal replication are determined by the binding of the AAA(+) protein DnaA to a set of high- and low-affinity sites found within the origin of chromosomal replication (oriC). Despite the large amount of information on the role and regulation of DnaA, the actual structure of the DnaA-oriC complex and the mechanism by which it primes the origin for the initiation of replication remain unclear. In this study, we have performed magnetic tweezers experiments to investigate the structural properties of the DnaA-oriC complex. We show that the DnaA-ATP-oriC complex adopts a right-handed helical conformation involving a variable amount of DNA and protein whose features fit qualitatively as well as quantitatively with an existing model based on the crystal structure of a truncated DnaA tetramer obtained in the absence of DNA. We also investigate the topological effect of oriC's DNA unwinding element.

Background/Purpose Skin mechanical properties are globally well described. The aim of this paper is to evaluate, by means of a numerical model, the influence of Stratum Corneum (SC) on skin folding resulting from an in-plane compression. Methods A computational skin model was developed where skin is divided into three layers (SC, epidermis and upper dermis, and deep dermis) of different thicknesses and elastic moduli. Skin surface deformation, consecutive to the application of a given surface compression, was computed by minimizing the mechanical energy of the multi-layered tissue. Influence of SC thickness and elastic modulus on skin buckling is presented. Results Varying both SC thickness and elastic modulus has a marked influence on both wavelength and amplitude of the skin's surface folds. These two parameters display a logarithmic variation versus SC elastic modulus. Conclusion Although representing about one hundredth of the total skin thickness, SC has a marked influence on the skin mechanical properties.

International audience; The structure of mouse atherosclerotic lesions may differ from that of humans, and mouse atherosclerotic plaques do not rupture except in some specific locations such as the brachiocephalic artery. Recently, our group was the first to observe that the amplitudes of in vivo stresses in ApoE-/- mouse aortic atherosclerotic lesions were much lower and differed from those found in a previous work performed on human lesions. In this previous preliminary work, we hypothesized that the plaque mechanical properties (MP) may in turn be responsible for such species differences. However, the limited number of human samples used in our previous comparative study was relevant but not sufficient to broadly validate such hypothesis. Therefore, in this study, we propose an original finite element strategy that reconstructs the in vivo stress/strain (IVS/S) distributions in ApoE-/- artherosclerotic vessels based on cross substitution of ApoE-/- mouse and human plaque components stiffnesses and including residual stress/strain (RS/S). Our results: (1) showed that including RS/S decreases by a factor 2 the amplitude of maximal IVS/S, and more importantly, (2) demonstrated that the MP of the ApoE-/- plaque constituents are mainly responsible for the low level-compared with human-of intraplaque stress in ApoE-/- mouse aortic atherosclerotic lesions (8.36 ± 2.63 kPa vs. 182.25 ± 55.88 kPa for human). Our study highlights that such differences in the distribution and amplitude of vessel wall stress might be one key feature for explaining for the difference in lesion stability between human coronary and mouse aortic lesions.

International audience; Cells are active materials; they can change shape using internal energy to build contractile networks of actin filaments and myosin motors. Contractility of the actomyosin cortex is tightly regulated in space and time to orchestrate cell shape changes. Conserved biochemical pathways regulate actomyosin networks in subcellular domains which drive cell shape changes. Actomyosin networks display complex dynamics, such as flows and pulses, which participate in myosin distribution and provide a more realistic description of the spatial distribution and evolution of forces during morphogenesis. Such dynamics are influenced by the mechanical properties of actomyosin networks. Moreover, actomyosin can self-organize and respond to mechanical stimuli through multiple types of biomechanical feedback. In this review we propose a framework encapsulating spatiotemporal regulation of contractility from established pathways with the dynamics and mechanics of actomyosin networks. Through the comparison of cytokinesis, cell migration and epithelial morphogenesis, we delineate emergent properties of contractile activity, including self-organization, adaptability and robustness.

International audience; The interaction of histone H1 with linker DNA results in the formation of the nucleosomal stem structure, with considerable influence on chromatin organization. In a recent paper [Syed,S.H., Goutte-Gattat,D., Becker,N., Meyer,S., Shukla,M.S., Hayes,J.J., Everaers,R., Angelov,D., Bednar,J. and Dimitrov,S. (2010) Single-base resolution mapping of H1-nucleosome interactions and 3D organization of the nucleosome. Proc. Natl Acad. Sci. USA, 107, 9620-9625], we published results of biochemical footprinting and cryo-electron-micrographs of reconstituted mono-, di- and tri-nucleosomes, for H1 variants with different lengths of the cationic C-terminus. Here, we present a detailed account of the analysis of the experimental data and we include thermal fluctuations into our nano-scale model of the stem structure. By combining (i) crystal and NMR structures of the nucleosome core particle and H1, (ii) the known nano-scale structure and elasticity of DNA, (iii) footprinting information on the location of protected sites on the DNA backbone and (iv) cryo-electron micrographs of reconstituted tri-nucleosomes, we arrive at a description of a polymorphic, hierarchically organized stem with a typical length of 20 ± 2 base pairs. A comparison to linker conformations inferred for poly-601 fibers with different linker lengths suggests, that intra-stem interactions stabilize and facilitate the formation of dense chromatin fibers.

Podosomes are dynamic, actin-containing adhesion structures that self-organize as rings in osteoclasts. We observe that podosome rings generate tension forces and that osteoclasts migrate by periodically moving toward the actin-containing structures. Actin dynamics thus not only correlate with the cell migration, but drive it., Podosomes are dynamic, actin-containing adhesion structures that collectively self-organize as rings. In this study, we first show by observing osteoclasts plated on bead-seeded soft substrates that podosome assemblies, such as rings, are involved in tension forces. During the expansion of a podosome ring, substrate displacement is oriented outward, suggesting that podosomal structures push the substrate away. To further elucidate the function of forces generated by podosomes, we analyze osteoclast migration. Determining the centers of mass of the whole cell (G) and of actin (P), we demonstrate that osteoclasts migrate by “jumps” and that the trajectories of G and P are strongly correlated. The velocity of the center of mass as a function of time reveals that osteoclasts rapidly catch up with podosomal structures in a periodic pattern. We conclude that actin dynamics inside the cell are not only correlated with cell migration, but drive it.

Coronary bifurcations represent specific regions of the arterial tree that are susceptible to atherosclerotic lesions. While the effects of vessel compliance, curvature, pulsatile blood flow, and cardiac motion on coronary endothelial shear stress have been widely explored, the effects of myocardial contraction on arterial wall stress/strain (WS/S) and vessel stiffness distributions remain unclear. Local increase of vessel stiffness resulting from wall-strain stiffening phenomenon (a local process due to the nonlinear mechanical properties of the arterial wall) may be critical in the development of atherosclerotic lesions. Therefore, the aim of this study was to quantify WS/S and stiffness in coronary bifurcations and to investigate correlations with plaque sites. Anatomic coronary geometry and cardiac motion were generated based on both computed tomography and MRI examinations of eight patients with minimal coronary disease. Computational structural analyses using the finite element method were subsequently performed, and spatial luminal arterial wall stretch (LWStretch) and stiffness (LWStiff) distributions in the left main coronary bifurcations were calculated. Our results show that all plaque sites were concomitantly subject to high LWStretch and high LWStiff, with mean amplitudes of 34.7 ± 1.6% and 442.4 ± 113.0 kPa, respectively. The mean LWStiff amplitude was found slightly greater at the plaque sites on the left main coronary artery (mean value: 482.2 ± 88.1 kPa) compared with those computed on the left anterior descending and left circumflex coronary arteries (416.3 ± 61.5 and 428.7 ± 181.8 kPa, respectively). These findings suggest that local wall stiffness plays a role in the initiation of atherosclerotic lesions.

Objective— Despite the fact that mechanical stresses are well recognized as key determinants for atherosclerotic plaque rupture, very little is known about stress amplitude and distribution in atherosclerotic lesions, even in the standard apolipoprotein E (apoE) −/− mouse model of atherosclerosis. Our objectives were to combine immunohistology, atomic force microscopy measurements, and finite element computational analysis for the accurate quantification of stress amplitude and distribution in apoE −/− mouse aortic atherosclerotic lesions. Methods and Results— Residual stresses and strains were released by radially cutting aortic arch segments from 7- to 30-week-old pathological apoE −/− (n=25) and healthy control mice (n=20). Immunohistology, atomic force microscopy, and biomechanical modeling taking into account regional residual stresses and strains were performed. Maximum stress values were observed in the normal arterial wall (276±71 kPa), whereas low values ( Conclusion— Low mechanical stress amplitude was observed in apoE −/− mouse aortic atherosclerotic lesions. This original study provides a basis for further investigations aimed at determining whether low stress levels are responsible for the apparently higher stability of murine aortic atherosclerotic lesions.

International audience; In the last decade, a lot of patents have been filled regarding molecular biology and functions of cellular membranes. The membrane bilayer model has evolved from a static, passive, homogeneous barrier to a highly dynamic, asymmetric, heterogeneous structure composed of distinct domains. Changes in membrane fluidity and composition of microdomains have been proven to be involved in the regulation of many important physiological signaling pathways. Recently, several xenobiotics, including various drugs and environmental pollutants, have been reported to change plasma membrane characteristics, thereby altering cell physiology. Interestingly, it has been suggested that a cross talk between chemical-induced cellular membrane effects and DNA damages may be important for the final mutation outcome of genotoxic chemicals. Thus, effects on plasma membrane remodeling may give additional mechanistic explanations to how certain chemicals exert their carcinogenic effect. With respect to such effects, recent patents suggest to focus on plasma membrane and its components like caveolin-1 for cancer screening and chemotherapy. Here, we review the effects of environmental toxicants on cellular plasma membrane structure and function, and further describe possible implication for health and disease.

Cisplatin is an antineoplastic drug, mostly documented to cause cell death through the formation of DNA adducts. In patients, it exhibits a range of short-term side effects that are unlikely to be related to its genomic action. As cisplatin has been shown to modify membrane properties in different cell systems, we investigated its effects on mechanosensitive ion transporters and channels. We show here that cisplatin is a noncompetitive inhibitor of the mechanosensitive Na+/H+ exchanger NHE-1, with a half-inhibition concentration of 30 μg/mL associated with a decrease in Vmax and Hill coefficient. We also showed that it blocks the Cl− and K+ mechanosensitive channels VSORC and TREK-1 at similar concentrations. In contrast, the nonmechanosensitive Cl− and K+ channels CFTR and TASK-1 and the Na+-coupled glucose transport, which share functional features with VSORC, TREK-1, and NHE-1, respectively, were insensitive to cisplatin. We next investigated whether cisplatin action was due to a direct effect on membrane or to cortical actin remodeling that would affect mechanosensors. Using scanning electron microscopy, in vivo actin labeling, and atomic force microscopy, we did not observe any modification of the Young's modulus and actin cytoskeleton for up to 60 and 120 μg/mL cisplatin, whereas these concentrations modified membrane morphology. Our results reveal a novel mechanism for cisplatin, which affects mechanosensitive channels and transporters involved in cell fate programs and/or expressed in mechanosensitive organs in which cisplatin elicits strong secondary effects, such as the inner ear or the peripheral nervous system. These results might constitute a common denominator to previously unrelated effects of this drug. Cancer Res; 70(19); 7514–22. ©2010 AACR.

International audience; Actin filaments are semiflexible polymers that display large-scale conformational twisting and bending motions. Modulation of filament bending and twisting dynamics has been linked to regulatory actin-binding protein function, filament assembly and fragmentation, and overall cell motility. The relationship between actin filament bending and twisting dynamics has not been evaluated. The numerical and analytical experiments presented here reveal that actin filaments have a strong intrinsic twist-bend coupling that obligates the reciprocal interconversion of bending energy and twisting stress. We developed a mesoscopic model of actin filaments that captures key documented features, including the subunit dimensions, interaction energies, helicity, and geometrical constraints coming from the double-stranded structure. The filament bending and torsional rigidities predicted by the model are comparable to experimental values, demonstrating the capacity of the model to assess the mechanical properties of actin filaments, including the coupling between twisting and bending motions. The predicted actin filament twist-bend coupling is strong, with a persistence length of 0.15-0.4 μm depending on the actin-bound nucleotide. Twist-bend coupling is an emergent property that introduces local asymmetry to actin filaments and contributes to their overall elasticity. Up to 60% of the filament subunit elastic free energy originates from twist-bend coupling, with the largest contributions resulting under relatively small deformations. A comparison of filaments with different architectures indicates that twist-bend coupling in actin filaments originates from their double protofilament and helical structure.

International audience; Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 ± 3.9% and 81.5 ± 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than ∼300 µm, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 ± 23.7 kPa instead of 145.4 ± 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young's moduli of 31.4 ± 9.7 kPa instead of 17.6 ± 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

Background— Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics. Methods and Results— In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity. Conclusions— CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT.

ERMA; International audience; The objective of this study was to evaluate the conditions of ankle stability and the morphological and/or lesional factors in sprains that determine when instability becomes chronic. It is based on a review of the literature and the data from the 2008 Sofcot symposium. The biomechanics of the ankle cannot be reduced to a simple flexion-extension movement with one degree of freedom as characterized by the talocrural joint: its function cannot be dissociated from the subtalar joint, allowing the foot to adapt to the ground surface. Functional stability is related to the combination of the particular biometry of the joint surfaces and a multiaxial ligament system. The bone morphology of the talus, shaped like a truncated cone, explains the potential instability in plantar flexion; the radii of curvature of the talar dome have a variable mediolateral distribution: most often the medial radius of curvature is inferior to the lateral radius of curvature (66%), sometimes equal (19%), or inverted (15%). Joint kinematics, combining rotation and slide, can therefore be modulated by the talar morphology, explaining the occurrence of at-risk ankles. Ligament stability relies on the organization in three parts of the lateral collateral ligament and the specific subtalar ligaments: the cervical and the talocalcaneal interosseous ligament. The different injury mechanisms are largely responsible for the sequence of ligament lesions: the most frequent is inversion. The first ligament stabilizers correspond to the cervical and anterior talofibular ligaments; the talocalcaneal ligament, by its oblique orientation, is solicited when there is a dorsal varus-flexion component. In chronic instability, these mechanisms explain the onset of associated lesions (impingement, osteochondral lesions, fibular tendon pathology), which can play a role in instability syndrome. Ligament lesions determine laxity, characteristic of mechanical instability. Functional instability goes along with proprioceptive deficiency. There are postural factors such as varus of the hindfoot that favor instability. Knowledge of all these factors, often associated, will provide a precise lesional assessment and treatment adapted to the instability.

International audience; Many techniques are described to treat Chiari type I malformation. One of them is a splitting of the dura, removing its outer layer only to reduce the risks of cerebrospinal fluid (CSF) leak. We try to show the effectiveness of this technique from histological and biomechanical observations of dura mater. Study was performed on 25 posterior fossa dura mater specimens from fresh human cadavers. Dural composition and architecture was assessed on 47 transversal and sagittal sections. Uniaxial mechanical tests were performed on 22 dural samples (15 entire, 7 split) to focus on the dural macroscopic mechanical behavior comparing entire and split samples and also to understand deformation mechanisms. We finally created a model of volume expansion after splitting. Dura mater was composed of predominant collagen fibers with a few elastin fibers, cranio-caudally orientated. The classical description of two distinct layers remained inconstant. Biomechanical tests showed a significant difference between entire dura, which presents an elastic fragile behavior, with a small domain where deformation is reversible with stress, and split dura, which presents an elasto-plastic behavior with a large domain of permanent strain and a lower stress level. From these experimental results, the model showed a volume increase of approximately 50% below the split area. We demonstrated the capability of the split dura mater to enlarge for suitable stress conditions and we quantified it by biomechanical tests and experimental model. Thus, dural splitting decompression seems to have a real biomechanical substrate to envision the efficacy of this Chiari type I malformation surgical technique.

International audience; OBJECTIVE: To analyze the role that biomechanical strains and psychosocial work factors play in occupational class disparities in low-back pain in the GAZEL cohort. METHODS: Recruited in 1989, the GAZEL cohort members were employees of the French national company in charge of energy who volunteered to enroll in an annual follow-up survey. The study population comprised 1487 men who completed questionnaires in 1996 (past occupational exposure to manual material handling, bending/twisting, and driving), 1997 (psychosocial work factors), and 2001 (low-back pain using a French version of the Nordic questionnaire for the assessment of low-back pain). Associations between low-back pain for >30 days in the preceding 12 months and social position at baseline (four categories) were described with a Cox model to determine prevalence ratios for each category. We compared adjusted and unadjusted ratios to quantify the contribution of occupational exposures. RESULTS: The prevalence of low-back pain for >30 days was 13.6%. The prevalence of low-back pain adjusted for age was significantly higher for blue-collar workers and clerks than for managers. The number of socioeconomic disparities observed was significantly reduced when biomechanical strains were taken into account; adjusting for psychosocial factors had little impact. CONCLUSION: In this population, occupational exposures--especially biomechanical strains--played an important role in occupational class disparities for persistent or recurrent low-back pain.

Background— Numerous studies have reported evidence of cardiac injury associated with transient left ventricular (LV) systolic and diastolic dysfunction after prolonged and strenuous exercise. We used 2D ultrasound speckle tracking imaging to evaluate the effect of an ultralong-duration exercise on LV regional strains and torsion. We speculated that systolic dysfunction after exercise is associated with depressed LV strains and torsion, and diastolic dysfunction results from decreased and delayed untwisting, a key factor of LV suction and early filling. Methods and Results— Twenty-three triathletes underwent conventional and speckle tracking imaging echocardiography at rest before and immediately after an ultralong distance triathlon. Measurements included LV longitudinal, circumferential and radial strains, LV rotations, and LV torsion. After the race, LV systolic dysfunction was characterized by a decrease in LV longitudinal, radial, and circumferential strains, especially for apical radial strains (44.6�15.1% versus 31.1�13.8%, P P =0.09) and significantly delayed (91�18% versus 128�31% of systolic duration, P Conclusions— This study documented major alterations in cardiac strains and torsion after an ultralong distance triathlon. LV systolic strains were depressed but not delayed, whereas twisting was decreased and delayed. This altered pattern hampered the rapid untwisting during isovolumic relaxation phase, reducing LV diastolic suction and early filling.

†Background and Aims Plants are likely to invest in multiple defences, given the variety of sources of biotic andabiotic damage to which they are exposed. However, little is known about syndromes of defence across plantspecies and how these differ in contrasting environments. Here an investigation is made into the associationbetween carbon-based chemical and mechanical defences, predicting that species that invest heavily in mechan-ical defence of leaves will invest less in chemical defence.†Methods A combination of published and unpublished data is used to test whether species with tougher leaveshave lower concentrations of phenolics, using 125 species from four regions of Australia and the Pacific island ofNew Caledonia, in evergreen vegetation ranging from temperate shrubland and woodland to tropical shrublandand rainforest. Foliar toughness was measured as work-to-shear and specific work-to-shear (work-to-shear perunit leaf thickness). Phenolics were measured as ‘total phenolics’ and by protein precipitation (an estimate oftannin activity) per leaf dry mass.†Key Results Contrary to prediction, phenolic concentrations were not negatively correlated with either measureof leaf toughness when examined across all species, within regions or within any plant community. Instead,measures of toughness (particularly work-to-shear) and phenolics were often positively correlated in shrublandand rainforest (but not dry forest) in New Caledonia, with a similar trend suggested for shrubland in south-western Australia. The common feature of these sites was low concentrations of soil nutrients, with evidenceof P limitation.†Conclusions Positive correlations between toughness and phenolics in vegetation on infertile soils suggest thatadditive investment in carbon-based mechanical and chemical defences is advantageous and cost-effective inthese nutrient-deficient environments where carbohydrate may be in surplus.Key words: Antiherbivore defence, leaf toughness, mechanical defence, chemical defence, phenolics, trade-offs.

Background Following stroke, patients frequently demonstrate loss of motor control and function and altered kinematic parameters of reaching movements. Feedback is an essential component of rehabilitation and auditory feedback of kinematic parameters may be a useful tool for rehabilitation of reaching movements at the impairment level. The aim of this study was to investigate the effect of 2 types of auditory feedback on the kinematics of reaching movements in hemiparetic stroke patients and to compare differences between patients with right (RHD) and left hemisphere damage (LHD). Methods 10 healthy controls, 8 stroke patients with LHD and 8 with RHD were included. Patient groups had similar levels of upper limb function. Two types of auditory feedback (spatial and simple) were developed and provided online during reaching movements to 9 targets in the workspace. Kinematics of the upper limb were recorded with an electromagnetic system. Kinematics were compared between groups (Mann Whitney test) and the effect of auditory feedback on kinematics was tested within each patient group (Friedman test). Results In the patient groups, peak hand velocity was lower, the number of velocity peaks was higher and movements were more curved than in the healthy group. Despite having a similar clinical level, kinematics differed between LHD and RHD groups. Peak velocity was similar but LHD patients had fewer velocity peaks and less curved movements than RHD patients. The addition of auditory feedback improved the curvature index in patients with RHD and deteriorated peak velocity, the number of velocity peaks and curvature index in LHD patients. No difference between types of feedback was found in either patient group. Conclusion In stroke patients, side of lesion should be considered when examining arm reaching kinematics. Further studies are necessary to evaluate differences in responses to auditory feedback between patients with lesions in opposite cerebral hemispheres.

International audience; An iterative solution to the inverse problem of elasticity and viscosity is proposed in this paper. A new dynamic finite element model that is consistent with known rheological models has been derived to account for the viscoelastic changes in soft tissue. The model assumes known lumped masses at the nodes, and comprises two vectors of elasticity and viscosity parameters that depend on the material elasticity and viscosity distribution, respectively. Using this deformation model and the observed dynamic data for harmonic excitation, the inverse problem is solved to reconstruct the viscosity and elasticity in the medium by using a Gauss-Newton-based approach. As in other inverse problems, previous knowledge of the parameters on the boundaries of the medium is necessary to assure uniqueness and convergence and to obtain an accurate map of the viscoelastic properties. The sensitivity of the solutions to noise, model and boundary conditions has been studied through numerical simulations. Experimental results are also presented. The viscosity and elasticity of a gelatin-based phantom with inclusion of known properties have been reconstructed and have been shown to be close to the values obtained using standard rheometry.

International audience; The constant bearing angle (CBA) strategy is a prospective strategy that permits the interception of moving objects. The purpose of the present study is to test this strategy. Participants were asked to walk through a virtual environment and to change, if necessary, their walking speed so as to intercept approaching targets. The targets followed either a rectilinear or a curvilinear trajectory and target size was manipulated both within trials (target size was gradually changed during the trial in order to bias expansion) and between trials (targets of different sizes were used). The curvature manipulation had a large effect on the kinematics of walking, which is in agreement with the CBA strategy. The target size manipulations also affected the kinematics of walking. Although these effects of target size are not predicted by the CBA strategy, quantitative comparisons of observed kinematics and the kinematics predicted by the CBA strategy showed good fits. Furthermore, predictions based on the CBA strategy were deemed superior to predictions based on a required velocity (V (REQ)) model. The role of target size and expansion in the prospective control of walking is discussed.

An important question in the literature focusing on motor control is to determine which laws drive biological limb movements. This question has prompted numerous investigations analyzing arm movements in both humans and monkeys. Many theories assume that among all possible movements the one actually performed satisfies an optimality criterion. In the framework of optimal control theory, a first approach is to choose a cost function and test whether the proposed model fits with experimental data. A second approach (generally considered as the more difficult) is to infer the cost function from behavioral data. The cost proposed here includes a term called the absolute work of forces, reflecting the mechanical energy expenditure. Contrary to most investigations studying optimality principles of arm movements, this model has the particularity of using a cost function that is not smooth. First, a mathematical theory related to both direct and inverse optimal control approaches is presented. The first theoretical result is the Inactivation Principle, according to which minimizing a term similar to the absolute work implies simultaneous inactivation of agonistic and antagonistic muscles acting on a single joint, near the time of peak velocity. The second theoretical result is that, conversely, the presence of non-smoothness in the cost function is a necessary condition for the existence of such inactivation. Second, during an experimental study, participants were asked to perform fast vertical arm movements with one, two, and three degrees of freedom. Observed trajectories, velocity profiles, and final postures were accurately simulated by the model. In accordance, electromyographic signals showed brief simultaneous inactivation of opposing muscles during movements. Thus, assuming that human movements are optimal with respect to a certain integral cost, the minimization of an absolute-work-like cost is supported by experimental observations. Such types of optimality criteria may be applied to a large range of biological movements., Author Summary When performing reaching and grasping movements, the brain has to choose one trajectory among an infinite set of possibilities. Nevertheless, because human and animal movements provide highly stereotyped features, motor strategies used by the brain were assumed to be optimal according to certain optimality criteria. In this study, we propose a theoretical model for motor planning of arm movements that minimizes a compromise between the absolute work exerted by the muscles and the integral of the squared acceleration. We demonstrate that under these assumptions agonistic and antagonistic muscles are inactivated during overlapping periods of time for quick enough movements. Moreover, it is shown that only this type of criterion can predict these inactivation periods. Finally, experimental evidence is in agreement with the predictions of the model. Indeed, we report the existence of simultaneous inactivation of opposing muscles during fast vertical arm movements. Therefore, this study suggests that biological movements partly optimize the energy expenditure, integrating both inertial and gravitational forces during the motor planning process.

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International audience; Findings from animal studies have suggested that bone remodeling is under beta-adrenergic control. However, the level of adrenergic inhibition required to achieve the most favorable effects on the skeleton remains unknown. To address this question, we compared the effects of low (0.1 mg/Kg/day), medium (5 mg/Kg/day) or high (20 mg/Kg/day) doses of propranolol given 5 days per week for 10 weeks in ovariectomized (OVX) rats. Characteristics of bone microarchitecture, biomechanical properties and bone turnover were investigated, whilst heart functions were assessed by echocardiography and catheterization of the left ventricle. We first confirmed the expression of Adrbeta2R and the absence of Adrbeta1R on osteoblasts by PCR and confocal microscopy. We then showed that low dose propranolol prevented OVX induced bone loss by increasing bone formation (+30% of MAR vs. placebo, P = 0.01) and decreasing bone resorption (-52% of osteoclast surface on bone surface vs. placebo, P = 0.01). Consequently, rats receiving 0.1 mg/kg/day propranolol displayed higher stress (+27%), intrinsic energy (+28.7%) and Young's Modulus in compression versus placebo (all, P < 0.05). No significant effects on heart hemodynamic parameters were found in rats receiving this dose. In contrast, medium and high doses of propranolol had a negative effect on heart functions but no significant protective effects on bone mass in ovariectomized rats. These results, consistent with the dominant nature of the high bone mass phenotype and normal heart function of Adrbeta2R-deficient mice, suggest that low doses of beta-blockers may have a therapeutic utility in the treatment of osteoporosis with high selectivity for bone tissues.

International audience; In this paper, we provide an update on cation channels in nucleated chicken erythrocytes. Patch-clamp techniques were used to further characterize the two different types of cation channels present in the membrane of chicken red blood. In the whole-cell mode, with Ringer in the bath and internal K+ saline in the pipette solution, the membrane conductance was generated by cationic currents, since the reversal potential was shifted toward cations equilibrium when the impermeant cation NMDG was substituted to small cations. The membrane conductance could be increased by application of mechanical deformation or by the addition of agonists of the cAMP-dependent pathway. At the unitary level, two different types of cationic channels were revealed and could account for the cationic conductance observed in whole-cell configuration. One of them belongs to the family of stretch-activated cationic channel showing changes in activity under conditions of membrane deformation, whereas the second one belongs to the family of the cAMP activated cationic channels. These two channels could be distinguished according to their unitary conductances and drug sensitivities. The stretch-activated channel was sensitive to Gd(3+) and the cAMP-dependent channel was sensitive to flufenamic acid. Possible role of these channels in cell volume regulation process is discussed.

Background and Purpose— To analyze the postural behavior of standing stroke patients: (1) To differentiate between postural impairment attributable to the neurological condition (deficits attributable to the cerebral lesion) and postural impairment attributable to new mechanical constraints caused by body weight asymmetry; (2) To assess the involvement of each limb in the postural impairment; (3) To better understand which clinical deficits underlie the postural impairment. Methods— The posturographic characteristics of each limb in 41 stroke patients (first hemispheric stroke: 16 left, 25 right cerebral lesions) required to stand in their preferred posture were compared to those in 40 matched healthy individuals required to stand asymmetrically. Results— Compared to normal individuals in a similar asymmetrical posture, stroke patients were more unstable. The weight bearing asymmetry and the lateral postural instability were mainly related to spatial neglect. The paretic limb was unable to bring into play a normal longitudinal pattern of the center of pressure, which reflects an impaired stabilization control. Overall postural instability occurred when the strong limb was unable to compensate for the postural impairment of the paretic limb. Conclusions— The weight bearing asymmetry of standing stroke patients is not the primary cause of their postural imbalance, which is rather the consequence of impaired control of postural stabilization involving both limbs. Weight bearing asymmetry may not be the principle target of rehabilitation programs aiming at restoring standing balance after stroke. Instead it is suggested that more account should be taken of the compensatory role of the strong limb.

In order to study both the hunting efficiency and the flexibility of their predatory behavior, solitary hunters of the trap-jaw ant Odontomachus opaciventris were offered small prey (termites, fruit flies and tenebrionid larvae), presenting different morphological or defensive characteristics. The monomorphic hunters showed a moderately flexible predatory behavior characterized by short capture sequences and a noteworthy efficiency of their mandible strike (76.7-100% of prey retrievals), even when presented with Nasutitermes soldiers. Contrary to most poneromorph ants, antennal palpation of the prey before the attack was always missing, no particular targeted region of the prey's body was preferred, and no 'prudent' posture was ever exhibited. Moreover, stinging was regularly performed on bulky, fast moving fruit flies, very scarcely with sclerotized tenebrionid larvae, but never occurred with Nasutitermes workers or soldiers despite their noxious chemical defense. These results suggest that, whatever the risk linked to potentially dangerous prey, O. opaciventris predatory strategy optimizes venom use giving top priority to the swiftness and strength of the lethal trap-jaw system used by hunters as first strike weapon to subdue rapidly a variety of small prey, ranging from 0.3 to 2 times their own body size and from 0.1 to 2 times their weight. Such risk-prone predatory behavior is likely to be related to the large size of O. opaciventris colonies where the death of a forager might be of lesser vital outcome than in small colony-size species.

International audience; OBJECTIVE: To assess the effects of duration of exposure to biomechanical strains on various types of low back pain (LBP). METHODS: The population study was a random sample from the GAZEL cohort. Durations of exposure to selected biomechanical strains during subjects' working lifetime and potential confounders were assessed in 1996 by self-administered questionnaires. Data on LBP in the previous 12 months were collected in 2001. Relations between various dimensions of LBP and durations of exposure to the biomechanical strains were analysed with multivariate regression models. Polytomous models were built to determine whether some biomechanical strains were specifically associated with some types of LBP. RESULTS: Analyses were performed separately for men (n = 2218) and women (n = 383). Significant associations were observed (ORs reported are those for 20 years of exposure) between LBP and durations of driving and bending/twisting for men (OR 1.24 and 1.37 respectively); LBP for more than 30 days and duration of exposure to bending/twisting for men and women (OR 2.20 and 2.00 respectively) and duration of driving for women (OR 3.15); LBP radiating to the leg and duration of driving for men (OR 1.43) and bending/twisting for women (OR 1.95); LBP radiating below the knee and duration of exposure to pulling/pushing/carrying for men (OR 1.88). Bending/twisting in both men and women, and driving for women appeared to be stronger risk factors for LBP for more than 30 days. Pulling/pushing/carrying heavy loads appeared to be a risk factor specific for LBP radiating below the knee for men. CONCLUSION: This study suggests that exposure to biomechanical strains has long-term effects and a dose-response relation with duration of exposure and specific effects for some types of LBP.

Many models that have been developed for cortical bone oversimplify much of the architectural and physical complexity. With SiNuPrOs model, a more complete approach is investigated: it is multiscale because it contains five structural levels and multi physic because it takes into account simultaneously structure (with various properties: elasticity, piezoelectricity, porous medium), fluid and mineralization process modelization. The multiscale aspect is modeled by using 18 structural parameters in a specific application of the mathematical theory of homogenization and 10 other physical parameters are necessary for the multi physic aspect. The modelization of collagen as a piezoelectric medium has needed the development of a new behaviour law allowing a better simulation of the effect of a medium considered as evolving during a mineralization process. Then the main interest of SiNuPrOs deals with the possibility to study, at each level of the cortical architecture, either the elastic properties or the fluid motion or the piezoelectric effects or both of them. All these possibilities constitute a very large work and all this mass of information (fluid aspects, even at the nanoscopic scale, piezoelectric phenomena and simulations) will be presented in several papers. This first one is only devoted to the presentation of this model with an application to the computation of elastic properties at the macroscopic scale. The computational methods have been packed into software also called SiNuPrOs and allowing a large number of predictive simulations corresponding to various different configurations.

International audience; Cell adhesion and migration are strongly influenced by extracellular matrix (ECM) architecture and rigidity, but little is known about the concomitant influence of such environmental signals to cell responses, especially when considering cells of similar origin and morphology, but exhibiting a normal or cancerous phenotype. Using micropatterned polydimethylsiloxane substrates (PDMS) with tunable stiffness (500 kPa, 750 kPa, 2000 kPa) and topography (lines, pillars or unpatterned), we systematically analyse the differential response of normal (3T3) and cancer (SaI/N) fibroblastic cells. Our results demonstrate that both cells exhibit differential morphology and motility responses to changes in substrate rigidity and microtopography. 3T3 polarisation and spreading are influenced by substrate microtopography and rigidity. The cells exhibit a persistent type of migration, which depends on the substrate anisotropy. In contrast, the dynamic of SaI/N spreading is strongly modified by the substrate topography but not by substrate rigidity. SaI/N morphology and migration seem to escape from extracellular cues: the cells exhibit uncorrelated migration trajectories and a large dispersion of their migration speed, which increases with substrate rigidity.

Using magnetic tweezers to investigate the mechanical response of single chromatin fibers, we show that fibers submitted to large positive torsion transiently trap positive turns, at a rate of one turn per nucleosome. A comparison with the response of fibers of tetrasomes (the (H3-H4)2 tetramer bound with ~50 bp of DNA) obtained by depletion of H2A-H2B dimers, suggests that the trapping reflects a nucleosome chiral transition to a metastable form built on the previously documented righthanded tetrasome. In view of its low energy, 33 pages (double spacing), 7 figures

International audience; Coordinated movements result from descending commands transmitted by central motor systems to the muscles. Although the resulting effect of the commands has the dimension of a muscular force, it is unclear whether the information transmitted by the commands concerns movement kinematics (e.g. position, velocity) or movement dynamics (e.g. force, torque). To address this issue, we used an optimal control model of movement production that calculates inputs to motoneurons that are appropriate to drive an articulated limb toward a goal. The model quantitatively accounted for kinematic, kinetic and muscular properties of planar, shoulder/elbow arm-reaching movements of monkeys, and reproduced detailed features of neuronal correlates of these movements in primate motor cortex. The model also reproduced qualitative spatio-temporal characteristics of movement- and force-related single neuron discharges in non-planar reaching and isometric force production tasks. The results suggest that the nervous system of the primate controls movements through a muscle-based controller that could be located in the motor cortex.

International audience; Vulnerable plaque morphology has been described by gross pathology and intravascular ultrasound, but morphological criteria cannot fully explain vulnerability, which involves four distinct factors: 1) inflammatory and biological processes; 2) geometry; 3) composition; and 4) hemodynamic stress. These last three aspects underlie the biomechanical study of vulnerable plaque. By virtue of the nature of their evolution, atherosclerotic plaques tend to be excentric, and this is a crucial morphological feature, causing circumferential stress to peak in very specific juxta-luminal locations, where it can exceed the rupture threshold of collagen, the basic constituent of arterial architecture. The lipido-necrotic core covered by a fibrous cap, formed in young plaques, is another morphological feature, which, can also increase and concentrate circumference stress in the juxta-luminal fibrous cap. The larger the lipid core, the thinner the fibrous cap and the greater is the stress. There are also inflammatory processes in such areas, which tend to reduce cap thickness. Ruptures occur when this thickness falls below 65 microns. Heart rate, blood pressure and pulse pressure are all biomechanical factors affecting vulnerable arterial walls, increasing circumferential stress and material fatigue. Vulnerable plaques are almost always associated with positive arterial remodeling. Numerical simulation has shown such so-called compensatory remodeling to be exclusively due to the healthy arc stretching in vulnerable plaques. Positive remodeling is optimal when the healthy arc is around 170 degrees, which keeps the lumen area relatively stable as long as the plaque does not exceed 40% to 50%. This mechanism does not apply to concentric plaques. In conclusion, the mechanism of vulnerable plaque rupture is highly complex and multifactorial. This complexity more or less precludes prediction in individual cases: we are in the realms of chaos theory and acute sensitivity to initial conditions. The greatest caution is therefore required in any attempt to predict rupture from diagnostic imagery, which provides only morphological data on plaque's nature.

This study examined age-related differences in the coordinative mechanism of the reach-to-grasp movement in three groups of children aged 6, 8, and 11 year, and in healthy adults. Three prehension conditions were manipulated: an unimanual and a bimanual self-driven tasks in which the reaching and grasping of the object were performed by participants, and a bimanual externally-driven task, in which the experimenter brought the object into the vicinity of the participant which grasped it. Classical kinematics data-peak velocities of the reaching and the grasping, the time to onset grip opening, maximum grip opening and grip closure-were calculated. Moreover, to obtain equivalent kinematics variables for all age groups, relative time to peak velocity (% of reaching duration), relative maximum grip opening (% of object size), and percentage of the four types of phase plans between reaching velocity and grip size have been calculated for each group of age. Our main results showed (1) a high variability at age 6, (2) an age-related change between the 6- and 8-year old for almost all of the dependent variables, and (3) a significant difference between the 11-year olds and adults. In summary, at 6 years, the interdependence between the reaching and grasping programs was unstable. A transitory feedback-based coordination between reaching and grasping appeared at 8 years of age. Finally, the adults' relationship between reaching and grasping was not attained at the age of 11.

International audience; The aim of this study is to identify the kinetic principal components involved in one-leg running vertical jumps, as well as the potential differences between specialists from different sports. The sample was composed of 25 regional skilled athletes who play different jumping sports (volleyball players, handball players, basketball players, high jumpers and novices), who performed a running one-leg jump. A principal component analysis was performed on the data obtained from the 200 tested jumps in order to identify the principal components summarizing the six variables extracted from the force-time curve. Two principal components including six variables accounted for 78 % of the variance in jump height. Running one-leg vertical jump performance was predicted by a temporal component (that brings together impulse time, eccentric time and vertical displacement of the center of mass) and a force component (who brings together relative peak of force and power, and rate of force development). A comparison made among athletes revealed a temporal-prevailing profile for volleyball players, and a force-dominant profile for Fosbury high jumpers. Novices showed an ineffective utilization of the force component, while handball and basketball players showed heterogeneous and neutral component profiles. Participants will use a jumping strategy in which variables related to either the magnitude or timing of force production will be closely coupled; athletes from different sporting backgrounds will use a jumping strategy that reflects the inherent demands of their chosen sport.

International audience; PURPOSE: The purpose of this study was to determine whether bisphosphonate treatment can prevent or delay osteocyte apoptosis in a cyclic fatigue animal model and if there are differences between two different bisphosphonates in their effects on osteocyte apoptosis. INTRODUCTION: Fatigue loading induces microdamage in long bones in rats and causes osteocyte apoptosis. In vitro data suggest that the bisphosphonates can prevent osteocyte apoptosis. MATERIALS AND METHODS: Six month old female Sprague-Dawley rats (n=72) were given a daily subcutaneous (sc) injection of saline vehicle, risedronate (RIS: 0.05 mug/kg per day) or alendronate (ALN: 0.1 mug/kg per day). On the 8th day of drug treatment, an axial compressive load was applied to the right ulna using a load-controlled electromagnetic device (17N, 6000 cycles, 2 Hz, 10% loss of stiffness approximately 1 h). Three, seven or ten days after loading, the animals were sacrificed. Immunohistochemistry for caspase-3 was performed to assess the extent of osteocyte apoptosis in loaded and non-loaded ulnas. RESULTS: Microdamage (Mdx) created by cyclic loading of the ulna induced a significant increase (p=0.03) in the number of apoptotic osteocytes compared to non-damaged regions of the same ulna, and compared to the contralateral non-loaded ulna. Risedronate and alendronate had an early effect (3 days after loading) on reducing load-induced osteocyte apoptosis. Risedronate significantly reduced the density of apoptotic osteocytes compared to vehicle-treated controls by approximately 50% in the Mdx area, whereas alendronate reduced it by approximately 40%. There were no differences among groups by seven days following loading. CONCLUSIONS: (1) Low doses of risedronate or alendronate suppressed osteocyte apoptosis induced by fatigue loading of the ulna in rats. (2) There was no difference between the effects of risedronate or alendronate on osteocyte apoptosis at these doses.