Search

Microrobots that can move through a network of blood vessels have promising medical applications. Blood contains a high volume fraction of blood cells, so in order for a microrobot to move through the blood, it must propel itself by rearranging the surrounding blood cells. However, swimming form effective for propulsion in blood is unknown. This study shows numerically that a surface-active microrobot, such as a squirmer, is more efficient in moving through blood than an inert microrobot. This is because the surface velocity of the microrobot steers the blood cells laterally, allowing them to propel themselves into the hole they are digging. When the microrobot size is comparable to a red blood cell or when the microrobot operates under a low Capillary number, the puller microrobot swims faster than the pusher microrobot. The trend reverses under considerably smaller microrobot sizes or high Capillary number scenarios. Additionally, the swimming speed is strongly dependent on the hematocrit and magnetic torque used to control the microrobot orientation. A comparative analysis between the squirmer and Janus squirmer models underscores the extensive applicability of the squirmer model. The obtained results provide new insight into the design of microrobots propelled efficiently through blood, paving the way for innovative medical applications., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Revealing the mechanisms of glucose transport is crucial for studying pathological diseases caused by glucose toxicities. Numerous studies have revealed molecular functions involved in glucose transport in the nematode Caenorhabditis elegans, a commonly used model organism. However, the behavior of glucose in the intestinal lumen-to-cell remains elusive. To address that, we evaluated the diffusion coefficient of glucose in the intestinal apical brush border of C. elegans by using fluorescent glucose and fluorescence recovery after photobleaching. Fluorescent glucose taken in the intestine of worms accumulates in the apical brush border, and its diffusion coefficient of ∼10 -8 cm 2 /s is two orders of magnitude slower than that in bulk. This result indicates that the intestinal brush border is a viscous layer. ERM-1 point mutations at the phosphorylation site, which shorten the microvilli length, did not significantly affect the diffusion coefficient of fluorescent glucose in the brush border. Our findings imply that glucose enrichment is dominantly maintained by the viscous layer composed of the glycocalyx and molecular complexes on the apical surface., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The gut microbiota, vital for host health, influences metabolism, immune function, and development. Understanding the dynamic processes of bacterial accumulation within the gut is crucial, as it is closely related to immune responses, antibiotic resistance, and colorectal cancer. We investigated Escherichia coli behavior and distribution in zebrafish larval intestines, focusing on the gut microenvironment., Results: We discovered that E. coli spread was considerably suppressed within the intestinal folds, leading to a strong physical accumulation in the folds. Moreover, a higher concentration of E. coli on the dorsal side than on the ventral side was observed. Our in vitro microfluidic experiments and theoretical analysis revealed that the overall distribution of E. coli in the intestines was established by a combination of physical factor and bacterial taxis., Conclusions: Our findings provide valuable insight into how the intestinal microenvironment affects bacterial motility and accumulation, enhancing our understanding of the behavioral and ecological dynamics of the intestinal microbiota., (© 2024. The Author(s).)

The endotracheal tubes (ETTs) used for children have a smaller inner diameter. Accordingly, the resistance across ETT (R ETT ) is higher. Theoretically, shortening the ETTs can decrease total airway resistance (R total ), because R total is sum of R ETT and patient's airway resistance. However, the effectiveness of ETT shortening for mechanical ventilation in the clinical setting has not been reported. We assessed the effectiveness of shortening a cuffed ETT for decreasing R total , and increasing tidal volume (TV), and estimated the R ETT /R total ratio in children. In anesthetized children in a constant pressure-controlled ventilation setting, R total and TV were measured with a pneumotachometer before and after shortening a cuffed ETT. In a laboratory experiment, the pressure gradient across the original length, shortened length, and the slip joint alone of the ETT were measured. We then determined the R ETT /R total ratio using the above results. The clinical study included 22 children. The median ETT percent shortening was 21.7%. Median R total was decreased from 26 to 24 cmH 2 O/L/s, and median TV was increased by 6% after ETT shortening. The laboratory experiment showed that ETT length and the pressure gradient across ETT are linearly related under a certain flow rate, and approximately 40% of the pressure gradient across the ETT at its original length was generated by the slip joint. Median R ETT /R total ratio were calculated as 0.69. The effectiveness of ETT shortening on R total and TV was very limited, because the resistance of the slip joint was very large., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The paired review papers in Parts I and II describe the 50-year history of research on the biomechanics of swimming microorganisms and its prospects in the next 50 years. Parts I and II are divided not by the period covered, but by the content of the research: Part I explains the behaviours of individual microorganisms, and Part II explains collective behaviour. In the 1990s, the description of microbial suspensions as a continuum progressed, and macroscopic flow structures such as bioconvection were analysed. The continuum model was later extended to analyse various phenomena such as flow induced trapping of microorganisms and accumulation of cells at interfaces. In the 2000s, the collective behaviour of swimming microorganisms came into the limelight, and physicists as well as biomechanics researchers carried out many studies probing microorganism collectivity. In particular, research on the turbulence-like flow structure of dense bacterial suspensions has led to dramatic developments in the field of microbial biomechanics. Efforts to bridge the cellular scale to the macroscopic scale by extracting macroscopic physical quantities from the microstructure of cell suspensions are also underway. This Part II reviews these collective behaviours of swimming microorganisms and discusses future prospects of the field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The recent discovery of the striking sheetlike multicellular choanoflagellate species Choanoeca flexa that dynamically interconverts between two hemispherical forms of opposite orientation raises fundamental questions in cell and evolutionary biology, as choanoflagellates are the closest living relatives of animals. It similarly motivates questions in fluid and solid mechanics concerning the differential swimming speeds in the two states and the mechanism of curvature inversion triggered by changes in the geometry of microvilli emanating from each cell. Here we develop fluid dynamical and mechanical models to address these observations and show that they capture the main features of the swimming, feeding, and inversion of C. flexa colonies, which can be viewed as active, shape-shifting polymerized membranes.

In mechanically ventilated severe acute respiratory distress syndrome patients, spontaneous inspiratory effort generates more negative pressure in the dorsal lung than in the ventral lung. The airflow caused by this pressure difference is called pendelluft, which is a possible mechanisms of patient self-inflicted lung injury. This study aimed to use computer simulation to understand how the endotracheal tube and insufficient ventilatory support contribute to pendelluft. We established two models. In the invasive model, an endotracheal tube was connected to the tracheobronchial tree with 34 outlets grouped into six locations: the right and left upper, lower, and middle lobes. In the non-invasive model, the upper airway, including the glottis, was connected to the tracheobronchial tree. To recreate the inspiratory effort of acute respiratory distress syndrome patients, the lower lobe pressure was set at -13 cmH2O, while the upper and middle lobe pressure was set at -6.4 cmH2O. The inlet pressure was set from 10 to 30 cmH2O to recreate ventilatory support. Using the finite volume method, the total flow rates through each model and toward each lobe were calculated. The invasive model had half the total flow rate of the non-invasive model (1.92 L/s versus 3.73 L/s under 10 cmH2O, respectively). More pendelluft (gas flow into the model from the outlets) was observed in the invasive model than in the non-invasive model. The inlet pressure increase from 10 to 30 cmH2O decreased pendelluft by 11% and 29% in the invasive and non-invasive models, respectively. In the invasive model, a faster jet flowed from the tip of the endotracheal tube toward the lower lobes, consequently entraining gas from the upper and middle lobes. Increasing ventilatory support intensifies the jet from the endotracheal tube, causing a venturi effect at the bifurcation in the tracheobronchial tree. Clinically acceptable ventilatory support cannot completely prevent pendelluft., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Takahashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The paired review papers in Parts I and II describe the 50-year history of research on the biomechanics of swimming microorganisms and its prospects in the next 50 years: Part I explains the behaviour of individual microorganisms, and Part II explains collective behaviour. Since the discovery of microorganisms by van Leeuwenhoek in the 17th century, many natural scientists have been interested in their motility because it is directly associated with biological function. A research upsurge occurred in the 1970s, with the elucidation of swimming mechanisms among individual microorganisms and the theoretical derivation of swimming speeds. Various swimming strategies of three types of microorganisms, i.e. bacteria, ciliates and microalgae, are explained in this Part I. We show that some of the behaviours of microorganisms can be described by biomechanical equations and are to some extent predictable. Recent researches have revealed the behaviour of microorganisms in more complex environments and more realistic settings, which are also reviewed in the paper. Last, we provide future prospects for research on microbial behaviour., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immotile cilia of crown cells at the node of mouse embryos are required for sensing leftward fluid flow that gives rise to the breaking of left-right (L-R) symmetry. The flow-sensing mechanism has long remained elusive, mainly because of difficulties inherent in manipulating and precisely analyzing the cilium. Recent progress in optical microscopy and biophysical analysis has allowed us to study the mechanical signals involving primary cilia. In this study, we used high-resolution imaging with mechanical modeling to assess the membrane tension in a single cilium. Optical tweezers, a technique used to trap sub-micron-sized particles with a highly focused laser beam, allowed us to manipulate individual cilia. Super-resolution microscopy allowed us to discern the precise localization of ciliary proteins. Using this protocol, we provide a method for applying these techniques to cilia in mouse embryonic nodes. This method is widely applicable to the determination of mechanical signals in other cilia., Competing Interests: Competing interestsThe authors declare no competing interests., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY-NC license.)

Immotile cilia at the ventral node of mouse embryos are required for sensing leftward fluid flow that breaks left-right symmetry of the body. However, the flow-sensing mechanism has long remained elusive. In this work, we show that immotile cilia at the node undergo asymmetric deformation along the dorsoventral axis in response to the flow. Application of mechanical stimuli to immotile cilia by optical tweezers induced calcium ion transients and degradation of Dand5 messenger RNA (mRNA) in the targeted cells. The Pkd2 channel protein was preferentially localized to the dorsal side of immotile cilia, and calcium ion transients were preferentially induced by mechanical stimuli directed toward the ventral side. Our results uncover the biophysical mechanism by which immotile cilia at the node sense the direction of fluid flow.

Despite its physiological and pathological importance, the mechanical relationship between glucose uptake in the intestine and intestinal flows is unclear. In the intestine of the nematode Caenorhabditis elegans, the defecation motor program (DMP) causes reciprocating intestinal flows. Although the DMP is frequently activated in the intestines, its physiological function is unknown. We evaluated the mechanical signature of enhanced glucose uptake by the DMP in worms. Glucose uptake tended to increase with increasing flow velocity during the DMP because of mechanical mixing and transport. However, the increase in input energy required for the DMP was low compared with the calorie intake. The findings suggest that animals with gastrointestinal motility exploit the reciprocating intestinal flows caused by peristalsis to promote nutrient absorption by intestinal cells., (© 2022. The Author(s).)

Competing Interests: Declaration of interests The author declares no competing interests.

Fluid mechanics show that high-density gases need more energy while flowing through a tube. Thus, high-density anesthetic gases consume more energy to flow and less energy for lung inflation during general anesthesia. However, its impact has not been studied. Therefore, this study aimed to investigate the effects of high-density anesthetic gases on tidal volume in laboratory and clinical settings. In the laboratory study, a test lung was ventilated at the same pressure-controlled ventilation with 22 different gas compositions (density range, 1.22-2.27 kg/m 3 ) using an anesthesia machine. A pneumotachometer was used to record the tidal volume of the test lung and the respiratory gas composition; it showed that the tidal volume of the test lung decreased as the respiratory gas density increased. In the clinical study, the change in tidal volume per body weight, accompanied by gas composition change (2% sevoflurane in oxygen and with 0-30-60% of N 2 O), was recorded in 30 pediatric patients. The median tidal volume per body weight decreased by 10% when the respiratory gas density increased from 1.41 kg/m 3 to 1.70 kg/m 3 , indicating a significant between-group difference (P < 0.0001). In both settings, an increase in respiratory gas density decreased the tidal volume during pressure-controlled ventilation, which could be explained by the fluid dynamics theory. This study clarified the detailed mechanism of high-density anesthetic gas reduced the tidal volume during mechanical ventilation and revealed that this phenomenon occurs during pediatric anesthesia, which facilitates further understanding of the mechanics of ventilation during anesthesia practice and respiratory physiology.

The Brazil nut effect (BNE) is a counter-intuitive process of segregation of a large object inside a vibrated granular medium (GM), which has been studied widely by subjecting GMs to various kinds of shears and vibrations. In this article, we report a new kind of BNE which occurs as a consequence of granular fluctuations induced by microbe-generated gas bubbles. We call it the 'microbial Brazil nut effect'. The paper demonstrates microbial BNE for a bidisperse granular mixture as well as for intruder segregation. Furthermore, using X-ray μCT and a simple scaling argument for segregation velocity, the paper clarifies the transport mechanics of an intruder inside a bubbly granular bed. We think the reported phenomenon should be ubiquitous in the microbe-populated wet sandy floors of waterbodies and may have some implication on the distribution of material near the floors.

To survive in harsh environments, single-celled microorganisms autonomously respond to external stimuli, such as light, heat, and flow. Here, we elucidate the flow response of Tetrahymena, a well-known single-celled freshwater microorganism. Tetrahymena moves upstream against an external flow via a behavior called rheotaxis. While micrometer-sized particles are swept away downstream in a viscous flow, what dynamics underlie the rheotaxis of the ciliate? Our experiments reveal that Tetrahymena slides along walls during upstream movement, which indicates that the cells receive rotational torque from shear flow to control cell orientation. To evaluate the effects of the shear torque and propelling speed, we perform a numerical simulation with a hydrodynamic model swimmer adopting cilia dynamics in a shear flow. The swimmer orientations converge to an upstream alignment, and the swimmer slides upstream along a boundary wall. The results suggest that Tetrahymena automatically responds to shear flow by performing rheotaxis using cilia-stalling mechanics.

Bacterial biofilms, which can be found wherever there is water and a substrate, can cause chronic infections and clogging of industrial flow systems. Despite intensive investigation of the dynamics and rheological properties of biofilms, the impact of their rheological properties on streamer growth remains unknown. We numerically simulated biofilm growth in a pillar-flow and investigated the effects of rheological properties of a filamentous flow-shaped biofilm, called a 'streamer', on its formation by varying the viscoelasticity. The flow-field is assumed to be a Stokes flow and is solved by a boundary element method. A Maxwell model is used for extracellular matrix-mediated streamer growth to express the fluidity of streamer formations. Both high elastic modulus and viscosity are needed for streamer formation, and high viscosity promotes streamer growth at low cell concentrations. Our findings are consistent with experimental observations and can explain the relationship between the cell concentrations and viscosity at which streamers form.

Given the ubiquity of bubbles and non-biodegradable wastes in aqueous environments, their transport through bubbles should be widely extant in water bodies. In this study, we investigate the effect of bubble-induced waste transport on microbial growth by using yeasts as model microbes and a silicone rubber object as model waste. Noteworthily, this object repeatedly rises and sinks in fluid through fluctuations in bubble-acquired buoyant forces produced by cyclic nucleation, growth and release of bubbles from object's surface. The rise-sink movement of the object gives rise to a strong bulk mixing and an enhanced resuspension of cells from the floor. Such spatially dynamic contaminant inside a nutrient-rich medium also leads to an increment in the total microbe concentration in the fluid. The enhanced concentration is caused by strong nutrient mixing generated by the object's movement which increases the nutrient supply to growing microbes and thereby, prolonging their growth phases. We confirm these findings through a theoretical model for cell concentration and nutrient distribution in fluid medium. The model is based on the continuum hypothesis and it uses the general conservation law which takes an advection-diffusion growth form. We conclude the study with the demonstration of bubble-induced digging of objects from model sand., (© 2021 The Authors.)

Cilia and centrosomes of eukaryotic cells play important roles in cell movement, fluid transport, extracellular sensing, and chromosome division. The physiological functions of cilia and centrosomes are generated by their dynamics, motions, and forces controlled by the physical, chemical, and biological environments. How an individual cilium achieves its beat pattern and induces fluid flow is governed by its ultrastructure as well as the coordination of associated molecular motors. Thus, a bottom-up understanding of the physiological functions of cilia and centrosomes from the molecular to tissue levels is required. Correlations between the structure and motion can be understood in terms of mechanics. This review first focuses on cilia and centrosomes at the molecular level, introducing their ultrastructure. We then shift to the organelle level and introduce the kinematics and mechanics of cilia and centrosomes. Next, at the tissue level, we introduce nodal ciliary dynamics and nodal flow, which play crucial roles in the organogenetic process of left-right asymmetry. We also introduce respiratory ciliary dynamics and mucous flow, which are critical for protecting the epithelium from drying and exposure to harmful particles and viruses, i.e., respiratory clearance function. Finally, we discuss the future research directions in this field., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Planktonic microorganisms are ubiquitous in water, and their population dynamics are essential for forecasting the behavior of global aquatic ecosystems. Their population dynamics are strongly affected by these organisms' motility, which is generated by their hair-like organelles, called cilia or flagella. However, because of the complexity of ciliary dynamics, the precise role of ciliary flow in microbial life remains unclear. Here, we have used ciliary hydrodynamics to show that ciliates acquire the optimal propulsion efficiency. We found that ciliary flow highly resists an organism's propulsion and that the swimming velocity rapidly decreases with body size, proportional to the power of minus two. Accordingly, the propulsion efficiency decreases as the cube of body length. By increasing the number of cilia, however, efficiency can be significantly improved, up to 100-fold. We found that there exists an optimal number density of cilia, which provides the maximum propulsion efficiency for all ciliates. The propulsion efficiency in this case decreases inversely proportionally to body length. Our estimated optimal density of cilia corresponds to those of actual microorganisms, including species of ciliates and microalgae, which suggests that now-existing motile ciliates and microalgae have survived by acquiring the optimal propulsion efficiency. These conclusions are helpful for better understanding the ecology of microorganisms, such as the energetic costs and benefits of multicellularity in Volvocaceae, as well as for the optimal design of artificial microswimmers., Competing Interests: The authors declare no competing interest.

Bubble-induced transport is a ubiquitous natural and industrial phenomenon. In brewery, such transport occurs due to gas bubbles generated through anaerobic fermentation by yeasts. Two major kinds of fermentation viz. top (ale) and bottom (lager) fermentation, display a difference in their yeast distributions inside a sugar broth. The reason for this difference is believed to be yeast-bubble adhesion arising due to surface hydrophobicity of the yeast cell wall; however, the physical mechanism is still largely a mystery. In this report, through in vivo experiments, we develop a novel theoretical model for yeast distribution based on the general conservation law. This work clarifies that bubble-induced diffusion is the dominant transport mechanism in bottom-fermentation by lagers whereas, yeast-bubble adhesion plays a leading role in transporting ales in top-fermentation, thereby corroborating the centuries-old belief regarding distribution difference in yeast population in two kinds of fermentation.

Bacteria inhabit a variety of locations and play important roles in the environment and health. Our understanding of bacterial biomechanics has improved markedly in the last decade and has revealed that biomechanics play a significant role in microbial biology. The obtained knowledge has enabled investigation of complex phenomena, such as biofilm formation and the dynamics of the gut flora. A bottom-up strategy, i.e., from the cellular to the macroscale, facilitates understanding of macroscopic bacterial phenomena. In this Review, we first cover the biomechanics of individual bacteria in the bulk liquid and on surfaces as the base of complex phenomena. The collective behaviors of bacteria in simple environments are next introduced. We then introduce recent advances in biofilm biomechanics, in which adhesion force and the flow environment play crucial roles. We also review transport phenomena in the intestine and the dynamics of the gut flora, focusing on that in zebrafish. Finally, we provide an overview of the future prospects for the field., (© 2020 Author(s).)

Skin barrier function is the battlefront for preventing permeation of harmful substances and infectious diseases. However, it can be destroyed by mechanical forces, as shown in many studies. Excess rubbing may increase the permeability of the skin to aqueous material. Although the skin barrier plays an important physiological role in humans, the vulnerability of skin to mechanical rubbing is poorly understood. Therefore, we investigated the effects of rubbing on the skin in vitro; skin damage was quantified by laser-induced fluorescence. Microscopic observation showed that keratinocytes in the stratum corneum sustained traumatic damage, which reduced the barrier function in that region. The permeability of the skin to an aqueous solution increased with rubbing frequency and load, and rubbing markedly reduced the barrier function of the stratum corneum. To understand the mechanisms underlying the skin damage, we developed a simple mathematical model assuming that the skin is a viscoelastic material. We hypothesized that the increased skin permeability was caused by the damage sustained by keratinocytes in the stratum corneum, and that the permeability was proportional to the time-averaged strain. Our theoretical results showed quantitative agreement with the experimental results and illustrated that rubbing and strain relaxation play key roles in rubbing-induced permeation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The nematode Caenorhabditis elegans is a filter feeder that lives in various viscous habitats such as soil, the intestines of slugs, and rotting materials such as fruits and stems. Caenorhabditis elegans draws in suspensions of bacteria and separates bacteria from water using the pharyngeal pump. Although these worms often live in highly viscous habitats, it is still unclear how they survive in these environments by eating bacteria. In this study, we investigated the effects of suspension viscosity on the survival rate of malnourished worms by combining live imaging and scaling analyses. We found that survival rate decreased with increases in viscosity because the high viscosity suppressed the amount of food ingested. The same tendency was found in two feeding-defective mutants, eat-6 ( ad46 7) and eat-6 ( ad997 ). We also found that the high viscosity weakened pump function, but the velocities in the pharynx were not zero, even in the most viscous suspensions. Finally, we estimated the amount of ingested food using scaling analyses, which provided a master curve of the experimental survival rates. These results illustrate that the survival rate of C. elegans worms is strongly dependent on the ingested bacteria per unit time associated with physical environments, such as the viscosity of food suspensions and the cell density of bacteria. The pump function of the C. elegans pharynx is not completely lost even in fluids that have 10 5 times higher viscosity than water, which may contribute to their ability to survive around the world in highly viscous environments., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Active fluids containing self-propelled particles are relevant for applications such as self-mixing, micropumping, and targeted drug delivery. With a confined boundary, active fluids can generate bulk flow inside the system, which has the potential to create self-propelled active matter. In this study, we propose that an active droplet is driven by a collective motion of enclosed microswimmers. We show that the droplet migrates via the flow field generated by the enclosed microswimmers; moreover, the locomotion direction depends on the swimming mode of these internal particles. The locomotion mechanism of the droplet can be well explained by interfacial velocity, and the locomotion velocity shows good agreement with the Lighthill-Blake theory. These findings are essential to understand the interplay between the motion of self-propelled particles and the bulk motion response of active matter.

Random noise in low Reynolds number flow has rarely been used to obtain net migration of microscale objects. In this study, we numerically show that net migration of a microscale object can be extracted from random directional fluid forces in Stokes flow, by introducing deformability and inhomogeneous density into the object. We also developed a mathematical framework to describe the deformation-induced migration caused by noise. These results provide a basis for understanding the noise-induced migration of a microswimmer and are useful for harnessing energy from low Reynolds number flow.

Transport in gut is important, not only for digestion, metabolism, and nutrient uptake, but also for microbiotic circumstance in the digestive tract; however, the effects of mixing and pumping in the intestine have not been fully clarified. Therefore, in this study, we quantitatively explored intestinal mixing and pumping, represented using a dispersion coefficient and pressure rise in zebrafish larvae, which is a model organism for vertebrate digestive studies, over time by measuring transport phenomena after feeding. Here we provide the first quantitative evidence of the roles of anterograde and retrograde intestinal peristalses in the larval fish of Danio rerio after feeding in terms of digestive pumping and mixing functions by an in vivo imaging of intestinal propagation waves in the larval intestine. Peristaltic velocities in the anterior and posterior intestines change considerably after feeding for 5 h, while the intervals and amplitudes remain almost constant. The intestinal transport is successively visualized after feeding to elimination. Moreover, the particle tracking velocimetry in the chyme leads our quantitative understanding of outstanding mixing and pumping functions in the anterior and posterior intestines by adopting physical parameters of diffusivity and pressure rise, respectively. From scaling analysis, we found that the anterior intestine maintains mixing for 5 h from feeding, whereas the posterior intestine activates gradually pumping up. These results suggest that time change of pumping and mixing functions of intestinal peristalsis could considerably influence the nutrient uptake and microbiotic circumstance in the larval fish intestine. NEW & NOTEWORTHY Transport in gut is important, not only for digestion, metabolism, and nutrient uptake, but also for microbiotic circumstance; however, hydrodynamic effects in the intestine have not been fully clarified. We provide the first quantitative evidence of the mechanical roles of anterograde and retrograde intestinal peristalses in the larval fish of Danio rerio by adopting physical parameters of diffusivity and pressure rise. The intestine transitionally regulates mixing and pumping functions by peristaltic propagations after feeding.

The way the unicellular, biflagellated, green alga Chlamydomonas orients upward has long been discussed in terms of both mechanics and physiology. In this study, we focus on the mechanics, i.e. the 'passive' mechanisms, of gravitaxis. To rotate the body upwards, cellular asymmetry is critical. Chlamydomonas can be depicted as a nearly spherical cell body with two anterior, symmetric flagella. The present study looks at the question of whether the existence of the flagella significantly affects torque generation in upward reorientation. The 'density asymmetry model' assumes that the cell is spherical and bottom-heavy and that the shape and weight of the flagella are negligible, while the 'shape asymmetry model' considers the shape of the flagella. Both our experimental and simulation results revealed a considerable contribution from shape asymmetry to the upward orientation of Chlamydomonas reinhardtii , which was several times larger than that of density asymmetry. From the experimental results, we also quantified the extent of bottom-heaviness, i.e. the distance between the centers of gravity and the figure when the cell body is assumed to be spherical. Our estimation was approximately 30 nm, only one-third of previous assumptions. These findings indicate the importance of the viscous drag of the flagella to the upward orientation, and thus negative gravitaxis, in Chlamydomonas ., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Green algae of the Volvocine lineage, spanning from unicellular Chlamydomonas to vastly larger Volvox, are models for the study of the evolution of multicellularity, flagellar dynamics, and developmental processes. Phototactic steering in these organisms occurs without a central nervous system, driven solely by the response of individual cells. All such algae spin about a body-fixed axis as they swim; directional photosensors on each cell thus receive periodic signals when that axis is not aligned with the light. The flagella of Chlamydomonas and Volvox both exhibit an adaptive response to such signals in a manner that allows for accurate phototaxis, but in the former the two flagella have distinct responses, while the thousands of flagella on the surface of spherical Volvox colonies have essentially identical behavior. The planar 16-cell species Gonium pectorale thus presents a conundrum, for its central 4 cells have a Chlamydomonas-like beat that provide propulsion normal to the plane, while its 12 peripheral cells generate rotation around the normal through a Volvox-like beat. Here we combine experiment, theory, and computations to reveal how Gonium, perhaps the simplest differentiated colonial organism, achieves phototaxis. High-resolution cell tracking, particle image velocimetry of flagellar driven flows, and high-speed imaging of flagella on micropipette-held colonies show how, in the context of a recently introduced model for Chlamydomonas phototaxis, an adaptive response of the peripheral cells alone leads to photoreorientation of the entire colony. The analysis also highlights the importance of local variations in flagellar beat dynamics within a given colony, which can lead to enhanced reorientation dynamics.

Biomembranes feature phospholipid bilayers and serve as the interface between cells or organelles and the extracellular and/or cellular environment. Lipids can move freely throughout the membrane; the lipid bilayer behaves like a fluid. Such fluidity is important in terms of the actions of membrane transport proteins, which often mediate biological functions; membrane protein motion has attracted a great deal of attention. Because the proteins are small, diffusion phenomena are often in play, but flow-induced transport has rarely been addressed. Here, we used a dissipative particle dynamics approach to investigate flow-induced membrane protein transport. We analyzed the drift of a membrane protein located within a vesicle. Under the influence of shear flow, the protein gradually migrated toward the vorticity axis via a random walk, and the probability of retention around the axis was high. To understand the mechanism of protein migration, we varied both shear strength and protein size. Protein migration was induced by the balance between the drag and thermodynamic diffusion forces and could be represented by the Péclet number. These results improve our understanding of flow-induced membrane protein transport., (Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

We report a new technique for the high time-resolved depth measurement of molecular concentration distribution in a permeable hydrogel film with micro-depth precision. We developed an inclined observation technique in a laser-induced fluorescence (LIF) system, based on confocal microscopy, which measures the concentration distribution in the depth direction at less than micrometre intervals. The focal plane of confocal microscopy was tilted to enable simultaneous depth scanning in the microscopic field of view inside the permeable substrate. Our system achieved real-time and non-contact depth measurement of concentration distribution in the permeable hydrogel film. Simultaneous depth concentration measurement was realised with < 1 μm/pixel resolution over a maximum depth range of 570 μm, depending on the tilt angle of the stage and optical conditions. Our system measured the concentration of fluorescence materials based on the fluorescence intensities at several depth positions with a minimum concentration resolution of 1.3 nmol/L. Applying the proposed system to real-time concentration imaging, we successfully visualised unsteady concentration transport phenomena, and estimated the mass transport coefficient through the liquid-hydrogel interface. Our findings are useful for investigating the mass transport of physical, biological, and medical phenomena in permeable substrates., Competing Interests: The authors have declared that no competing interests exist.

The interactions of bacteria with surfaces have important implications in numerous areas of research, such as bioenergy, biofilm, biofouling, and infection. Recently, several experimental studies have reported that the adhesion of bacteria can be reduced considerably by microscale wall features. To clarify the effect of wall configurations, we numerically investigated the behavior of swimming bacteria near a flat wall with a bump line. The results showed that the effects of bump configuration are significant; a detachment time larger than several seconds can be achieved in certain parameter sets. These results illustrate that the number density of bacteria near the wall may be reduced by appropriately controlling the parameter sets. When background shear flow was imposed, the near-wall bacterium mainly moved towards the vorticity axis. The detachment time of cells increased significantly by adjusting the bump line to have 45^{∘} relative to the flow direction. The knowledge obtained in this study is fundamental for understanding the interactions between bacteria and surfaces according to more complex geometries, and is useful for reducing the adhesion of cells to walls.

It has been suggested that the swimming mechanism used by spermatozoa could be adopted for self-propelled micro-robots in small environments and potentially applied to biomedical engineering. Mammalian sperm cells must swim through a viscoelastic mucus layer to find the egg cell. Thus, understanding how sperm cells swim through viscoelastic liquids is significant not only for physiology, but also for the design of micro-robots. In this paper, we developed a numerical model of a sperm cell in a linear Maxwell fluid based on the boundary element slender-body theory coupling method. The viscoelastic properties were characterized by the Deborah number ( De ), and we found that, under the prescribed waveform, the swimming speed decayed with the Deborah number in the small- De regime ( De < 1.0). The swimming efficiency was independent of the Deborah number, and the decrease in the swimming speed was not significantly affected by the wave pattern.

A squirmer model achieves propulsion by generating surface squirming velocities. This model has been used to analyze the movement of micro-swimmers, such as microorganisms and Janus particles. Although squirmer motion has been widely investigated, motions of two connected squirmers, i.e., a dumbbell squirmer, remain to be clarified. The stable assembly of multiple micro-swimmers could be a key technology for future micromachine applications. Therefore, in this study, we investigated the swimming behavior and stability of a dumbbell squirmer. We first examined far-field stability through linear stability analysis, and found that stable forward swimming could not be achieved by a dumbbell squirmer in the far field without the addition of external torque. We then investigated the swimming speed of a dumbbell squirmer connected by a short rigid rod using a boundary element method. Finally, we investigated the swimming stability of a dumbbell squirmer connected by a spring. Our results demonstrated that stable side-by-side swimming can be achieved by pullers. When the aft squirmer was a strong pusher, fore and aft swimming were stable and swimming speed increased significantly. The findings of this study will be useful for the future design of assembled micro-swimmers., Competing Interests: The author declares no conflict of interest.

Some types of ciliates accumulate on solid/fluid interfaces. This behavior is advantageous to survival in nature due to the presence of sufficient nutrition and stable environments. Recently, the accumulating mechanisms of Tetrahymena pyriformis at the interface were investigated. The synergy of the ellipsoidal shape of the cell body and the mechanosensing feature of the cilia allow for cells to slide on interfaces, and the sliding behavior leads to cell accumulation on the interfaces. Here, to examine the generality of the sliding behavior of ciliates, we characterized the behavior of Paramecium caudatum , which is a commonly studied ciliate. Our experimental and numerical results confirmed that P. caudatum also slid on the solid/fluid interface by using the same mechanism as T. pyriformis . In addition, we evaluated the effects of cellular ellipticity on their behaviors near the wall with a phase diagram produced via numerical simulation.

Left-right (L-R) asymmetry in the body plan is determined by nodal flow in vertebrate embryos. Shinohara et al. (Shinohara K et al. 2012 Nat. Commun. 3 , 622 (doi:10.1038/ncomms1624)) used Dpcd and Rfx3 mutant mouse embryos and showed that only a few cilia were sufficient to achieve L-R asymmetry. However, the mechanism underlying the breaking of symmetry by such weak ciliary flow is unclear. Flow-mediated signals associated with the L-R asymmetric organogenesis have not been clarified, and two different hypotheses-vesicle transport and mechanosensing-are now debated in the research field of developmental biology. In this study, we developed a computational model of the node system reported by Shinohara et al. and examined the feasibilities of the two hypotheses with a small number of cilia. With the small number of rotating cilia, flow was induced locally and global strong flow was not observed in the node. Particles were then effectively transported only when they were close to the cilia, and particle transport was strongly dependent on the ciliary positions. Although the maximum wall shear rate was also influenced by ciliary position, the mean wall shear rate at the perinodal wall increased monotonically with the number of cilia. We also investigated the membrane tension of immotile cilia, which is relevant to the regulation of mechanotransduction. The results indicated that tension of about 0.1 μN m -1 was exerted at the base even when the fluid shear rate was applied at about 0.1 s -1 . The area of high tension was also localized at the upstream side, and negative tension appeared at the downstream side. Such localization may be useful to sense the flow direction at the periphery, as time-averaged anticlockwise circulation was induced in the node by rotation of a few cilia. Our numerical results support the mechanosensing hypothesis, and we expect that our study will stimulate further experimental investigations of mechanotransduction in the near future., Competing Interests: We declare we have no competing interests.

The artificial microswimmer is a cutting-edge technology with applications in drug delivery and micro-total-analysis systems. The flow field around a microswimmer can be regarded as Stokes flow, in which reciprocal body deformation cannot induce migration. In this study, we propose a microcapsule swimmer that undergoes amoeboidlike shape deformations under fluid oscillation conditions. This is a study on the propulsion principle using a capsule with a solid membrane, and one of only a few studies using fluid oscillation. The microswimmer consists of an elastic capsule containing fluid and a rigid sphere. Opposing forces are generated when fluid oscillations are applied, because the densities of the internal fluid and sphere are different. The opposing forces induce nonreciprocal body deformation, which leads to migration of the microswimmer under Stokes flow conditions. Using numerical simulations, we found that the microswimmer propels itself in one of two modes, i.e., stroke swimming or drag swimming. We discuss the feasibility of the proposed microswimmer and show that the most efficient swimmer can migrate tens of micrometers per second. These findings pave the way for future artificial microswimmer designs.

Microbial flora in the intestine has been thoroughly investigated, as it plays an important role in the health of the host. Jemielita et al. (2014) showed experimentally that Aeromonas bacteria in the intestine of zebrafish larvae have a heterogeneous spatial distribution. Although bacterial aggregation is important biologically and clinically, there is no mathematical model describing the phenomenon and its mechanism remains largely unknown. In this study, we developed a computational model to describe the heterogeneous distribution of bacteria in the intestine of zebrafish larvae. The results showed that biological taxis could cause the bacterial aggregation. Intestinal peristalsis had the effect of reducing bacterial aggregation through mixing function. Using a scaling argument, we showed that the taxis velocity of bacteria must be larger than the sum of the diffusive velocity and background bulk flow velocity to induce bacterial aggregation. Our model and findings will be useful to further the scientific understanding of intestinal microbial flora., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

An important habit of ciliates, namely, their behavioral preference for walls, is revealed through experiments and hydrodynamic simulations. A simple mechanical response of individual ciliary beating (i.e., the beating is stalled by the cilium contacting a wall) can solely determine the sliding motion of the ciliate along the wall and result in a wall-preferring behavior. Considering ciliate ethology, this mechanosensing system is likely an advantage in the single cell's ability to locate nutrition. In other words, ciliates can skillfully use both the sliding motion to feed on a surface and the traveling motion in bulk water to locate new surfaces according to the single "swimming" mission., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Due to recent advances in micro total analysis system technologies, microfluidics provides increased opportunities to manipulate, stimulate, and diagnose blood cells. Controlling the concentration of cells at a given position across the width of a channel is an important aspect in the design of microfluidic devices. Despite its biomedical importance, the collective spreading of red blood cells (RBCs) in a microchannel has not yet been fully clarified. In this study, we experimentally investigated the collective spreading of RBCs in a straight microchannel, and found that RBCs initially distributed in one side of the microchannel spread to the spanwise direction during downstream flow. Spreading increased considerably as the hematocrit increased, though the flow rate had a small effect. We proposed a scaling argument to show that this spreading phenomenon was diffusive and mainly induced by cell-cell interactions. The dispersion coefficient was approximately proportional to the flow rate and the hematocrit. These results are useful in understanding collective behaviors of RBCs in a microchannel and in microcirculation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To gain insight into the nature of biological synchronization at the microscopic scale, we here investigate the hydrodynamic synchronization between conically rotating objects termed nodal cilia. A mechanical model of three rotating cilia is proposed with consideration of variation in their shapes and geometrical arrangement. We conduct numerical estimations of both near-field and far-field hydrodynamic interactions, and we apply a conventional averaging method for weakly coupled oscillators. In the nonidentical case, the three cilia showed stable locked-phase differences around ±π/2. However, such phase locking also occurred with three identical cilia when allocated in a triangle except for the equilateral triangle. The effects of inhomogeneity in cilia shapes and geometrical arrangement on such asymmetric interaction is discussed to understand the role of biological variation in synchronization via hydrodynamic interactions.

Understanding the behaviours of swimming microorganisms in various environments is important for understanding cell distribution and growth in nature and industry. However, cell behaviour in complex geometries is largely unknown. In this study, we used Tetrahymena thermophila as a model microorganism and experimentally investigated cell behaviour between two flat plates with a small angle. In this configuration, the geometry provided a 'dead end' line where the two flat plates made contact. The results showed that cells tended to escape from the dead end line more by hydrodynamics than by a biological reaction. In the case of hydrodynamic escape, the cell trajectories were symmetric as they swam to and from the dead end line. Near the dead end line, T. thermophila cells were compressed between the two flat plates while cilia kept beating with reduced frequency; those cells again showed symmetric trajectories, although the swimming velocity decreased. These behaviours were well reproduced by our computational model based on biomechanics. The mechanism of hydrodynamic escape can be understood in terms of the torque balance induced by lubrication flow. We therefore conclude that a cell's escape from the dead end was assisted by hydrodynamics. These findings pave the way for understanding cell behaviour and distribution in complex geometries., (© 2018 The Authors.)

Objective: SIPA, which is mediated by vWF, is a key mechanism in arterial thrombosis under an abnormally high shear rate of blood flow. We investigated the influence of SIPA on thrombogenesis, focusing on alterations in blood flow at stenotic vessels., Methods: We carried out a computer simulation of thrombogenesis in stenotic vessels at three different injury positions (ie, upstream, apex, and downstream of the stenosis) to evaluate the effect of SIPA., Results: The results demonstrated that thrombus volume increased downstream of the stenosis. In particular, growth was enhanced significantly as blood flow velocity and severity of stenosis increased. The influence of SIPA was induced by continuous exposure to high shear rate; thus, SIPA had a greater effect from the apex to downstream of the stenosis along the vessel wall. The asymmetry of the impact of SIPA contributed to the distribution of the thrombus. Furthermore, we found that the degree of SIPA was prolonged in a stenotic vessel with a distal injury, whereas it was moderate with thrombus growth in a nonstenosed vessel. This occurred because platelets and vWF that underwent a high shear rate around the apex were transported to the region downstream of the stenosis., Conclusions: These results suggest that thrombus formation downstream of the stenosis is easily affected by SIPA and hemodynamics., (© 2017 John Wiley & Sons Ltd.)

Due to its transparency, the intestine of zebrafish larvae has been widely used in studies of gastrointestinal diseases and the microbial flora of the gut. However, transport phenomena in the intestine of zebrafish larvae have not been fully clarified. In this study, therefore, transport caused by peristaltic motion in the intestine of zebrafish larvae was investigated by numerical simulation. An anatomically realistic three-dimensional geometric model of the intestine at various times after feeding was constructed based on the experimental data of Field et al. (2009). The flow of digested chyme was analyzed using the governing equations of fluid mechanics, together with peristaltic motion and long-term contraction of the intestinal wall. The results showed that retrograde peristaltic motion was the main contributor to the mixing function. The dispersion caused by peristalsis over 30min was in the order of 10 -12 m 2 /s, which is greater than the Brownian diffusion of a sphere of 0.4µm diameter. In contrast, anterograde peristaltic motion contributed mainly to the pumping function. The pressure decrease due to peristalsis was in the order of millipascals, which may reduce the activation and maintenance heat of intestinal muscle. These findings enhance our understanding of the mixing and pumping functions of the intestine of zebrafish larvae., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mucous flow in a tracheal lumen is generated by the beat motion of ciliated cells to provide a clearance function by discharging harmful dust particles and viruses. Due to its physiological importance, the cilia-generated flow and the rheological properties of mucus have been investigated intensively. The effects of viscosity on the cilia-generated flow, however, have not been fully clarified. In this study, we measured bulk background velocity of ciliary flow using a micro particle tracking velocimetry method under various viscosity conditions in mice. The results showed that the flow velocity decreased as the increase with viscosity of ambient fluid. Moreover, no previous study has clarified the pump power generated by cilia, which provides important information with regard to understanding the molecular motor properties of cilia. Measurements of both the ciliary flow and the ciliary motion were conducted to determine the cilia pump power. Our results indicated that the cilia pump during the effective stroke did not drive the ciliary flow efficiently under high viscosity conditions; these findings are necessary to resolve the clearance function.

Whole slide imaging (WSI) is a useful tool for multi-modal imaging, and in our work, we have often combined WSI with darkfield microscopy. However, traditional darkfield microscopy cannot use a single condenser to support high- and low-numerical-aperture objectives, which limits the modality of WSI. To overcome this limitation, we previously developed a darkfield internal reflection illumination (DIRI) microscope using white light-emitting diodes (LEDs). Although the developed DIRI is useful for biological applications, substantial problems remain to be resolved. In this study, we propose a novel illumination technique called color DIRI. The use of three-color LEDs dramatically improves the capability of the system, such that color DIRI (1) enables optimization of the illumination color; (2) can be combined with an oil objective lens; (3) can produce fluorescence excitation illumination; (4) can adjust the wavelength of light to avoid cell damage or reactions; and (5) can be used as a photostimulator. These results clearly illustrate that the proposed color DIRI can significantly extend WSI modalities for biological applications., Competing Interests: Brendan Brinkman and Yoshihiro Kawano are employed by a commercial company: Olympus Corporation. Lorne D. Davies, Olympus America Inc. and Kawano have filed a US patent application entitled: WIDE FIELD MICROSCOPIC IMAGING SYSTEM AND METHOD (publication number US2012/0092477 published on April 19, 2012, date of filing October 18, 2010). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The relationship between gastric motility and the mixing of liquid food in the stomach was investigated with a numerical analysis. Three parameters of gastric motility were considered: the propagation velocity, frequency, and terminal acceleration of peristaltic contractions. We simulated gastric flow with an anatomically realistic geometric model of the stomach, considering free surface flow and moving boundaries. When a peristaltic contraction approaches the pylorus, retropulsive flow is generated in the antrum. Flow separation then occurs behind the contraction. The extent of flow separation depends on the Reynolds number (Re), which quantifies the inertial forces due to the peristaltic contractions relative to the viscous forces of the gastric contents; no separation is observed at low Re, while an increase in reattachment length is observed at high Re. While mixing efficiency is nearly constant for low Re, it increases with Re for high Re because of flow separation. Hence, the effect of the propagation velocity, frequency, or terminal acceleration of peristaltic contractions on mixing efficiency increases with Re., (Copyright © 2016 the American Physiological Society.)

A numerical analysis is presented of cell adhesion in capillaries whose diameter is comparable to or smaller than that of the cell. In contrast to a large number of previous efforts on leukocyte and tumor cell rolling, much is still unknown about cell motion in capillaries. The solid and fluid mechanics of a cell in flow was coupled with a slip bond model of ligand-receptor interactions. When the size of a capillary was reduced, the cell always transitioned to "bullet-like" motion, with a consequent decrease in the velocity of the cell. A state diagram was obtained for various values of capillary diameter and receptor density. We found that bullet motion enables firm adhesion of a cell to the capillary wall even for a weak ligand-receptor binding. We also quantified effects of various parameters, including the dissociation rate constant, the spring constant, and the reactive compliance on the characteristics of cell motion. Our results suggest that even under the interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin, which is mainly responsible for leukocyte rolling, a cell is able to show firm adhesion in a small capillary. These findings may help in understanding such phenomena as leukocyte plugging and cancer metastasis., (Copyright © 2016 the American Physiological Society.)

Cellular structures are hydrodynamically interconnected, such that force generation in one location can move distal structures. One example of this phenomenon is cytoplasmic streaming, whereby active forces at the cell cortex induce streaming of the entire cytoplasm. However, it is not known how the spatial distribution and magnitude of these forces move distant objects within the cell. To address this issue, we developed a computational method that used cytoplasm hydrodynamics to infer the spatial distribution of shear stress at the cell cortex induced by active force generators from experimentally obtained flow field of cytoplasmic streaming. By applying this method, we determined the shear-stress distribution that quantitatively reproduces in vivo flow fields in Caenorhabditis elegans embryos and mouse oocytes during meiosis II. Shear stress in mouse oocytes were predicted to localize to a narrower cortical region than that with a high cortical flow velocity and corresponded with the localization of the cortical actin cap. The predicted patterns of pressure gradient in both species were consistent with species-specific cytoplasmic streaming functions. The shear-stress distribution inferred by our method can contribute to the characterization of active force generation driving biological streaming.

In the past decade, numerical methods for the computational biomechanics of blood flow have progressed to overcome difficulties in diverse applications from cellular to organ scales. Such numerical methods may be classified by the type of computational mesh used for the fluid domain, into fixed mesh methods, moving mesh (boundary-fitted mesh) methods, and mesh-free methods. The type of computational mesh used is closely related to the characteristics of each method. We herein provide an overview of numerical methods recently used to simulate blood flow at macro and micro scales, with a focus on computational meshes. We also discuss recent progress in the multi-scale modeling of blood flow., (Copyright © 2015 Elsevier Ltd. All rights reserved.)