Search

Exogenous high-voltage pulses increase cell membrane permeability through a phenomenon known as electroporation. This process may also disrupt the cell cytoskeleton causing changes in cell contractility; however, the contractile signature of cell force after electroporation remains unknown. Here, single-cell forces post-electroporation are measured using suspended extracellular matrix-mimicking nanofibers that act as force sensors. Ten, 100 μs pulses are delivered at three voltage magnitudes (500, 1000, and 1500 V) and two directions (parallel and perpendicular to cell orientation), exposing glioblastoma cells to electric fields between 441 V cm-1 and 1366 V cm-1. Cytoskeletal-driven force loss and recovery post-electroporation involves three distinct stages. Low electric field magnitudes do not cause disruption, but higher fields nearly eliminate contractility 2-10 min post-electroporation as cells round following calcium-mediated retraction (stage 1). Following rounding, a majority of analyzed cells enter an unusual and unexpected biphasic stage (stage 2) characterized by increased contractility tens of minutes post-electroporation, followed by force relaxation. The biphasic stage is concurrent with actin disruption-driven blebbing. Finally, cells elongate and regain their pre-electroporation morphology and contractility in 1-3 h (stage 3). With increasing voltages applied perpendicular to cell orientation, we observe a significant drop in cell viability. Experiments with multiple healthy and cancerous cell lines demonstrate that contractile force is a more dynamic and sensitive metric than cell shape to electroporation. A mechanobiological understanding of cell contractility post-electroporation will deepen our understanding of the mechanisms that drive recovery and may have implications for molecular medicine, genetic engineering, and cellular biophysics.

Aligned extracellular matrix fibers enable fibroblasts to undergo myofibroblastic activation and achieve elongated shapes. Activated fibroblasts are able to contract, perpetuating the alignment of these fibers. This poorly understood feedback process is critical in chronic fibrosis conditions, including cancer. Here, using fiber networks that serve as force sensors, we identify “3D perpendicular lateral protrusions” (3D-PLPs) that evolve from lateral cell extensions named twines. Twines originate from stratification of cyclic-actin waves traversing the cell and swing freely in 3D to engage neighboring fibers. Once engaged, a lamellum forms and extends multiple secondary twines, which fill in to form a sheet-like PLP, in a force-entailing process that transitions focal adhesions to activated (i.e., pathological) 3D-adhesions. The specific morphology of PLPs enables cells to increase contractility and force on parallel fibers. Controlling geometry of extracellular networks confirms that anisotropic fibrous environments support 3D-PLP formation and function, suggesting an explanation for cancer-associated desmoplastic expansion., Padhi et al. employ nanofibers with controlled structure and alignment as an extra-cellular matrix model, on which they study the exertion of forces from adherent fibroblasts. Identifying force exerting 3D perpendicular lateral protrusions, authors describe a mechanism which leads to the contraction of parallel, neighbouring fibers, and the forces needed to move and align the neighbouring fibers. These findings have relevance in understanding cancer-associated desmoplastic expansion.

Laminated plate structures are analyzed by a discontinuous finite element method with emphasis on determining the transverse shear and normal stress components at the interface of adjacent layers accurately. A Consistent Orthogonal Basis Function Space is used for the interpolation of the displacement field and the traction field between two adjacent layers. The mass matrix of the laminated plate becomes diagonal. Moreover, it is observed that the basis functions are very similar to the vibration mode shapes, even through we do not solve any eigenvalue problem in their generation. These basis functions are uniquely determined by the structure's configuration and associated boundary conditions. The stress field between the layers can be accurately calculated, even for the region near the boundaries that might have sharp stress gradients. Several numerical examples are studied with different boundary conditions. The results for both the deformation and the stress components are compared with the traditional finite element method, especially in terms of the number of degrees-of-freedom (DOF) used in the proposed method and the classic FEM. It is observed that the proposed method is able to use a much fewer number of DOF than that of commercial FEM software (ANSYS etc) to obtain accurate solutions to both the deformation of the plate and the stress field between adjacent layers.

The second-order statistics of critical stress intensity factor (SIF) of single edge notched fiber reinforced composite plates with random system properties and subjected to uniaxial tensile loadin...

An algorithm that integrates Karhunen-Loeve expansion (KLE), nonlinear finite element method (NFEM), and a sampling technique to quantify the uncertainty is proposed to carry out random vibration a...

This study presents a new approach for the rapid transonic flutter analysis of large-aspect-ratio wings via a combination of time-linearized two-dimensional unsteady indicial functions and a databa...

Challenging issues for sandwich structures include accurately finding their frequencies and how the load transfers from face sheets to the core when their material stiffness ratio (FCSR) in either the axial or the transverse directions varies from 1 to 1 0 7 . Here we use both the equivalent single layer and the layer wise shear and normal deformable plate theories to analyze problems for rectangular plates of different thickness/length ratios. The Ritz method with Jacobi polynomials as basis functions is employed to numerically solve three-dimensional linear elasticity theory equations. Transverse stresses are calculated using a one-step stress recovery scheme. It is found that the FCSR in the transverse direction determines the minimum degree of complete polynomials in the thickness coordinate needed to accurately compute the lowest six frequencies and the transverse stresses. New results include the following: (i) the FCSR in the transverse direction has a greater influence than that in the axial direction on the computed frequencies and transverse stresses, and (ii) whereas both transverse normal and shear stresses in the core contribute to transmitting loads between the two face sheets for FCSR 3, however, only the former is effective for FCSR ≥ 105.

An algorithm that integrates Karhunen-Loeve expansion (KLE) and the finite element method (FEM) is proposed to perform non-stationary random vibration analysis of structures under excitations, represented by multiple random processes that are correlated in both time and spatial domains. In KLE, the auto-covariance functions of random excitations are discretized using orthogonal basis functions. The KLE for multiple correlated random excitations relies on expansions in terms of correlated sets of random variables reflecting the cross-covariance of the random processes. During the response calculations, the eigenfunctions of KLE used to represent excitations are applied as forcing functions to the structure. The proposed algorithm is applied to a 2DOF system, a 2D cantilever beam and a 3D aircraft wing under both stationary and non-stationary correlated random excitations. Two methods are adopted to obtain the structural responses: a) the modal method and b) the direct method. Both the methods provide the statistics of the dynamic response with sufficient accuracy. The structural responses under the same type of correlated random excitations are bounded by the response obtained by perfectly correlated and uncorrelated random excitations. The structural response increases with a decrease in the correlation length and with an increase in the correlation magnitude. The proposed methodology can be applied for the analysis of any complex structure under any type of random excitation.

With rapid growth in the complexity of large scale engineering systems, the application of multidisciplinary analysis and design optimization (MDO) in the engineering design process has garnered much attention. MDO addresses the challenge of integrating several different disciplines into the design process. Primary challenges of MDO include computational expense and poor scalability. The introduction of a distributed, collaborative computational environment results in better utilization of available computational resources, reducing the time to solution, and enhancing scalability. SORCER, a Java-based network-centric computing platform, enables analyses and design studies in a distributed collaborative computing environment. Two different optimization algorithms widely used in multidisciplinary engineering design-VTDIRECT95 and QNSTOP-are implemented on a SORCER grid. VTDIRECT95, a Fortran 95 implementation of D. R. Jones‟ algorithm DIRECT, is a highly parallelizable derivative-free deterministic global optimization algorithm. QNSTOP is a parallel quasi-Newton algorithm for stochastic optimization problems. The purpose of integrating VTDIRECT95 and QNSTOP into the SORCER framework is to provide load balancing among computational resources, resulting in a dynamically scalable process. Further, the federated computing paradigm implemented by SORCER manages distributed services in real time, thereby significantly speeding up the design process. Part 1 covers SORCER and the algorithms, Part 2 presents results for aircraft panel design with curvilinear stiffeners.

Traditional flying qualities metrics use first-order descriptors of the “classical” aircraft modes such as the phugoid, short-period, Dutch roll, etc. These modes are often difficult to distinguish...

This paper presents an efficient finite element approach to study the prestressed vibration mode results of a curvilinearly stiffened composite panel subjected to various in-plane loads. The present method models the plate and the stiffener separately, which allows the stiffener element nodes to not coincide with the plate shell-element nodes. The stiffness and mass matrices of a stiffener are transformed to those of the plate through the displacement compatibility conditions at the plate–stiffener interface via finite element interpolation. Convergence and validation studies have been conducted to verify the present method in the finite element vibration analysis by using the examples from the existing literature. Prestressed vibration mode results are examined for a stiffened composite panel with arbitrarily shaped composite stiffeners in the presence of the in-plane normal and shear loads. Numerical results show the possible benefits of using curvilinear stiffeners to improve the vibration response by ...

Cell migration is centrally involved in a myriad of physiological processes, including morphogenesis, wound healing, tissue repair, and metastatic growth. The bioenergetics that underlie migratory behavior are not fully understood, in part because of variations in cell culture media and utilization of experimental cell culture systems that do not model physiological connective extracellular fibrous networks. In this study, we evaluated the bioenergetics of C2C12 myoblast migration and force production on fibronectin-coated nanofiber scaffolds of controlled diameter and alignment, fabricated using a nonelectrospinning spinneret-based tunable engineered parameters (STEP) platform. The contribution of various metabolic pathways to cellular migration was determined using inhibitors of cellular respiration, ATP synthesis, glycolysis, or glucose uptake. Despite immediate effects on oxygen consumption, mitochondrial inhibition only modestly reduced cell migration velocity, whereas inhibitors of glycolysis and cellular glucose uptake led to striking decreases in migration. The migratory metabolic sensitivity was modifiable based on the substrates present in cell culture media. Cells cultured in galactose (instead of glucose) showed substantial migratory sensitivity to mitochondrial inhibition. We used nanonet force microscopy to determine the bioenergetic factors responsible for single-cell force production and observed that neither mitochondrial nor glycolytic inhibition altered single-cell force production. These data suggest that myoblast migration is heavily reliant on glycolysis in cells grown in conventional media. These studies have wide-ranging implications for the causes, consequences, and putative therapeutic treatments aimed at cellular migration.

Metformin has been shown to alter cell adhesion protein expression, which is thought to play a role in its observed antitumor properties. We found that metformin treatment down-regulated integrin β1 concomitant with the loss of inositol polyphosphate multikinase (IPMK) in murine myocytes, adipocytes, and hepatocytes. To determine if IPMK was upstream of integrin β1 expression, we examined IPMK(−/−) mouse embryonic fibroblast cells and found that integrins β1 and β3 gene expression was reduced by half, relative to wild-type cells, whereas focal adhesion kinase (FAK) activity and Rho/Rac/Cdc42 protein levels were increased, resulting in migration defects. Using nanonet force microscopy, we determined that cell:extracellular matrix adhesion and cell contractility forces were decreased, confirming the functional relevance of integrin and Rho protein dysregulation. Pharmacological studies showed that inhibition of both FAK1 and proline-rich tyrosine kinase 2 partially restored integrin β1 expression, suggesting negative regulation of integrin β1 by FAK. Together our data indicate that IPMK participates in the regulation of cell migration and provides a potential link between metformin and wound healing impairment.—Tu-Sekine, B., Padhi, A., Jin, S., Kalyan, S., Singh, K., Apperson, M., Kapania, R., Hur, S. C., Nain, A., Kim, S. F. Inositol polyphosphate multikinase is a metformin target that regulates cell migration.

The variable-angle-tow (VAT) fiber path laminates are known to shift the maximum in-plane stress resultants away from the composite laminated panel’s center to the panel’s supported edges for improving the buckling response when compared to the traditional laminates. However, the improvement in the structural performance could be counteracted due to the fiber placement head turning radius and gaps/overlaps induced thickness variation in the VAT manufacturing process. The present paper investigates the effect of the minimal turning radius on the buckling load of a stiffened VAT laminated plate subjected to an axial in-plane end-shortening. Different laminate fiber path angles are parameterized and studied. Optimization studies show that when there is no manufacturing constraint, there is a significant increase in the buckling load, up to 20.5% and 44.0%, respectively, by using the stiffened VAT laminates with linearly and nonlinearly varying fiber path angles. The optimal linearly- and nonlinearly-varying fiber paths are found to be almost perpendicular to the stiffeners in the panel’s center and almost be parallel to the stiffeners near the panel’s free-load support edges. The present minimal fiber placement head turning radius has a significant effect on the buckling load improvement for the stiffened VAT laminated plates. There are only 6% and 7% increases in the total buckling load for the present stiffened composite plates with linearly- and nonlinearly-varying fiber path angles laminates, respectively, when considering the fiber curvature constraint.

Aligned extracellular matrix fibers impart an elongated cell morphology and enable fibroblasts to undergo myofibroblastic activation. Yet the biomechanical intricacies that are associated with this microenvironmental phenomenon are unknown. Here, we identify a new role of lateral protrusions, originating anywhere along elongated fibroblastic cells, which apply fiber-deflecting contractile forces. Using aligned fiber networks that serve as force sensors, we quantitate the role of lateral nano-projections (twines) that mature into “perpendicular lateral protrusions” (PLPs) through the formation of twine-bridges, thus allowing elongated cells to spread laterally and effectively contract. Using quantitative microscopy at high spatiotemporal resolution, we show that twines of varying lengths can originate from stratification of cyclic actin waves traversing along the entire length of the cell. Primary twines swing freely in 3D and engage with neighboring extracellular fibers in interaction times of seconds. Once engaged, an actin lamellum grows along the length of primary twine and re-stratifies to form a secondary twine. Engagement of secondary twine with the neighboring fiber leads to the formation of twine-bridge, a critical step in providing a conduit for actin to advance along and populate the twine-bridge. Through arrangement of fiber networks in varying configurations, we confirm that anisotropic fibrous environments are fertile for PLP dynamics, and importantly force-generating PLPs are oriented perpendicular to the parent cell body. Furthermore, cell spreading onto multiple fibers and myofibroblastic-like contraction occur through PLPs. Our identification of force exertion by PLPs identifies a possible explanation for cancer-associated desmoplastic expansion, at single-cell resolution, thus providing new clinical intervention opportunities.

An important objective for the aerospace industry is to design robust and fuel efficient aerospace structures. Advanced manufacturing techniques like additive manufacturing have allowed structural designers to make use of curvilinear stiffeners for achieving better designs of stiffened plate and shell structures. Finite Element Analysis (FEA) based standard optimization methods for aircraft panels with arbitrary curvilinear stiffeners are computationally expensive. The main reason for employing many of these standard optimization methods is the ease of their integration with FEA. However, each optimization requires multiple computationally expensive FEA evaluations, making their use impractical at times. To accelerate optimization, the use of Deep Neural Networks (DNNs) is proposed to approximate the FEA buckling response, computed using MSC NASTRAN. The finite element model of a plate is verified with those found in the literature. Later, a Python script is used to generate a large data-set using parallel processing. The 80%, 10% and 10% of the generated data-set are used for training, validation and testing of DNNs, respectively. The results show that DNNs, optimized using Adam optimizer, obtained an accuracy of 95% on the test set for approximating FEA response within 10% of the actual value. To compare the efficiency of the DNN, the trained DNN is used in the optimization of curvilinearly stiffened panels by replacing the conventional FEA. The DNN accelerated the optimization by a factor of nearly 200. The presented work demonstrates the potential of DNN-based machine learning algorithms for accelerating the optimization of curvilinearly stiffened panels.

Cell fragments devoid of the nucleus play an essential role in intercellular communication. Mostly studied on flat 2D substrates, their origins and behavior in native fibrous environments remain unknown. Here, cytoplasmic fragments’ spontaneous formation and behavior in suspended extracellular matrices mimicking fiber architectures (parallel, crosshatch, and hexagonal) are described. After cleaving from the parent cell body, the fragments of diverse shapes on fibers migrate faster compared to 2D. Furthermore, while fragments in 2D are mostly circular, a higher number of rectangular and blob-like shapes are formed on fibers, and, interestingly, each shape is capable of forming protrusive structures. Absent in 2D, fibers’ fragments display oscillatory migratory behavior with dramatic shape changes, sometimes remarkably sustained over long durations (>20 h). Immunostaining reveals paxillin distribution along fragment body-fiber length, while Forster Resonance Energy Transfer imaging of vinculin reveals mechanical loading of fragment adhesions comparable to whole cell adhesions. Using nanonet force microscopy, the forces exerted by fragments are estimated, and peculiarly small area fragments can exert forces similar to larger fragments in a Rho-associated kinase dependent manner. Overall, fragment dynamics on 2D substrates are insufficient to describe the mechanosensitivity of fragments to fibers, and the architecture of fiber networks can generate entirely new behaviors.

A stochastic extended finite element method (SXFEM), developed previously by the first two authors, has been extended for the fracture analysis along with reliability analysis of the central cracked laminated composite plate subjected to uni-axial tension with random system properties. The implemented SXFEM approach is based on the M -integral interaction combined with second-order perturbation technique (SOPT) and independent Monte Carlo simulation (MCS) is performed for the evaluation of statistics of mixed mode stress intensity factors (MMSIFs). The random system properties such as material properties, crack length, crack angle, lamination angle, and uni-axial loading, are assumed as input uncorrelated Gaussian random variables. The effect of the different crack angles, crack lengths, lamination angles, and loading on the statistics of MMSIF in terms of mean, standard deviation (SD), probability density function (PDF) and safety factor of cracked laminated composite plate is examined along with the reliability analysis. The effect of crack propagation and its direction along with its effect on the MMSIFs is carried out through global tracking crack growth algorithm. The results obtained by present approach, are compared with an analytical solution and results available in various literature.

This study investigates the effects of a variable-geometry raked wingtip on the aeroelastic behavior and the maneuverability of transport aircraft with very large aspect-ratio truss-braced wings. These truss-braced wing designs are obtained from the multidisciplinary design optimization environment presented here while minimizing the fuel burn of a double-aisle aircraft having a flight mission similar to that of a Boeing 777-200 long-range aircraft. The wingtip can be swept forward and aft relative to the wing by a novel control effector mechanism. Results show that a variable-geometry raked wingtip can be used to achieve required roll control by judiciously sweeping it relative to the wing at various flight conditions. It has an added benefit that it can also be used for flutter avoidance. Such benefits of the variable-geometry raked wingtip allow the operation of truss-braced wing configurations, which have up to 10% lower fuel burn than comparable optimized conventional cantilever wing designs. Without...

The structural optimization of a cantilever aircraft wing with stiffeners and curvilinear spars and ribs is described. The decomposition technique for the wing structure is widely used for the optimization of a complex wing. The optimization procedure is divided into two subsystems: the global wing optimization, which determines the geometry and location of spars and ribs, and local panel optimization to further reduce wing weight. Because the design variables that are changed in the global step have an impact on those changed in the local step and vice versa, an iterative process that iterates between the global and local optimizations is employed. Particle swarm optimization and gradient-based optimization are used to perform integrated global/local optimization. Parallel computing is used, implemented using Python, to reduce the central processing unit time. The license cycle-check method and memory self-adjustment method are developed and applied in the parallel processing framework to optimize the us...

We have performed a design optimization of a stiffened panel with curvilinear stiffeners using an artificial neural network (ANN) residual kriging based surrogate modeling approach. The ANN residual kriging based surrogate modeling involves two steps. In the first step, we approximate the objective function using ANN. In the next step we use kriging to model the residue. We optimize the panel in an iterative way. Each iteration involves two steps-shape optimization and size optimization. For both shape and size optimization, we use ANN residual kriging based surrogate model. At each optimization step, we do an initial sampling and fit an ANN residual kriging model for the objective function. Then we keep updating this surrogate model using an adaptive sampling algorithm until the minimum value of the objective function converges. The comparison of the design obtained using our optimization scheme with that obtained using a traditional genetic algorithm (GA) based optimization scheme shows satisfactory agreement. However, with this surrogate model based approach we reach optimum design with less computation effort as compared to the GA based approach which does not use any surrogate model.

An algorithm that integrates Karhunen–Loeve expansion (KLE) and finite element method (FEM) is proposed to carry out random vibration analysis of complex dynamic systems excited by stationary or non-stationary random processes. In KLE, the auto-covariance function of random process is discretized using orthogonal basis functions. During the response calculations, the eigenvectors of KLE are applied as forcing functions. Three methods are proposed to carry out the random vibration analysis termed as, Method 1A, Method 1B and Method 2. In Method 1A and Method 1B, the basis functions are chosen such that they include multiples of complete or half-cosine and sine functions over the selected time. In Method 2, the basis functions are chosen to be simple piecewise constants. The proposed algorithm is applied to a 2DOF system, a cantilever beam and a stiffened panel for both stationary and non-stationary excitations. Results show that three methods can describe the statistics of the dynamic response with sufficient accuracy. However, Method 1A results have a relatively larger error than that for Method 1B and Method 2 during initial transient time. The Method 2 results have an excellent agreement with analytical results. Moreover, the runtime of Method 2 algorithm is significantly less than both Method 1A and Method 1B algorithms even though its usage results in an increase in the number of KLE terms. Furthermore, Method 2, unlike Method 1A and 1B, neither yields negative and/or infinite eigenvalues for the auto-covariance function nor large inaccuracies.

Motivated by the need for high-fidelity modeling and accurate control of future hypersonic vehicles subjected to complex aerothermomechanical loads and many other such applications, a novel scheme is proposed to accurately compute higher modes of vibration for one-dimensional structures by coupling the classic Ritz method as a predictor and the linear two-point boundary value problem solver SUPORE as a corrector. The Ritz method is used to compute a preliminary estimate of the natural frequencies for the desired modes. These estimates are then used as initial guesses by SUPORE, which employs superposition and reorthonormalization to accurately solve the governing boundary value problem. Compared to a high-fidelity Ritz approximation or a highly refined finite element modeling procedure, this is a simple, computationally less expensive, and yet highly accurate method to compute mode shapes for applications that require higher modes. This scheme is used to compute mode shapes within an absolute and relative...

We investigated the natural frequencies and mode shapes of a freely vibrating, integrally stiffened and/or stepped plate. The stiffeners used here were plate-strip stiffeners as opposed to the normally employed rib stiffeners. Both the plate and stiffeners were analyzed using the first-order shear deformation theory. The deflections and rotations were assumed as a tensor product of Timoshenko beam functions, chosen appropriately according to the given boundary conditions. Unlike Navier and Levy solution techniques, the approach used in this paper can also be applied to fully clamped, free, and cantilever supported stiffened plates. The governing differential equations were solved using the Rayleigh–Ritz method. The development of the stiffness and the mass matrices in the Ritz analysis was found to consume a huge amount of CPU time due to recursive integration of Timoshenko beam functions. An approach is suggested to greatly decrease this amount of CPU time, by replacing the recursive integration in a loo...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

This paper finds up to lowest 100 free vibration frequencies of isotropic and linearly elastic plates with thickness to side length ratio varying from 0.001 to 0.5 by using the Ritz method, a third-order shear and normal deformable plate theory (TSNDT), and weighted Jacobi polynomials as admissible functions that are mutually orthogonal and exactly satisfy essential boundary conditions. The numerical method is stable even for 18th degree polynomials as basis functions. It is shown that this approach requires fewer degrees of freedom than those in the traditional finite element method (FEM) to find converged lowest 100 frequencies and the corresponding mode shapes. No shear correction factor is employed in the TSNDT. The presently computed results agree well with those from either analytical or numerical solutions of the corresponding 3-dimensional linearly elastic problems obtained with the commercial FE software, Abaqus. Furthermore, results for plates made of an incompressible material can be computed by setting Poisson's ratio = 0.49.