During mesenchymal migration, F-actin protrusion at the leading edge and actomyosin contraction determine the retrograde flow of F-actin within the lamella. The coupling of this flow to integrin-based adhesions determines the force transmitted to the extracellular matrix and the net motion of the cell. In tissues, motion may also arise from convection, driven by gradients in tissue-scale surface tensions and pressures. However, how migration coordinates with convection to determine the net motion of cellular ensembles is unclear. To explore this, we study the spreading of cell aggregates on adhesive micropatterns on compliant substrates. During spreading, a cell monolayer expands from the aggregate towards the adhesive boundary. However, cells are unable to stabilize the protrusion beyond the adhesive boundary, resulting in retraction of the protrusion and detachment of cells from the matrix. Subsequently, the cells move upwards and rearwards, yielding a bulk convective flow towards the centre of the aggregate. The process is cyclic, yielding a steady-state balance between outward (protrusive) migration along the surface, and ‘retrograde’ (contractile) flows above the surface. Modelling the cell aggregates as confined active droplets, we demonstrate that the interplay between surface tension-driven flows within the aggregate, radially outward monolayer flow and conservation of mass leads to an internal circulation.

The organization of actin filaments (F-actin) into crosslinked networks determines the transmission of mechanical stresses within the cytoskeleton and subsequent changes in cell and tissue shape. Principally mediated by proteins such as α-actinin, F-actin crosslinking increases both network connectivity and rigidity, thereby facilitating stress transmission at low crosslinking yet attenuating transmission at high crosslinker concentration. Here, we engineer a two-dimensional model of the actomyosin cytoskeleton, in which myosin-induced mechanical stresses are controlled by light. We alter the extent of F-actin crosslinking by the introduction of oligomerized cofilin. At pH 6.5, F-actin severing by cofilin is weak, but cofilin bundles and crosslinks filaments. Given its effect of lowering the F-actin bending stiffness, cofilin- crosslinked networks are significantly more flexible and softer in bending than networks crosslinked by α-actinin. Thus, upon local activation of myosin-induced contractile stress, the network bends out-of-plane in contrast to the in-plane compression as observed with networks crosslinked by α-actinin. Here, we demonstrate that local effects on filament mechanics by cofilin introduces novel large-scale network material properties that enable the sculpting of complex shapes in the cell cytoskeleton.

The invasive potential of glioblastoma cells is attributed to large changes in pressure and volume, driven by diverse elements, including the cytoskeleton and ion cotransporters. However, how the cell actuates changes in pressure and volume in confinement, and how these changes contribute to invasive motion is unclear. Here, we inhibited SPAK activity, with known impacts on the cytoskeleton and cotransporter activity and explored its role on the migration of glioblastoma cells in confining microchannels to model invasive spread through brain tissue. First, we found that confinement altered cell shape, inducing a transition in morphology that resembled droplet interactions with a capillary vessel, from “wetting” (more adherent) at low confinement, to “nonwetting” (less adherent) at high confinement. This transition was marked by a change from negative to positive pressure by the cells to the confining walls, and an increase in migration speed. Second, we found that the SPAK pathway impacted the migration speed in different ways dependent upon the extent of wetting. For nonwetting cells, SPAK inhibition increased cell-surface tension and cotransporter activity. By contrast, for wetting cells, it also reduced myosin II and YAP phosphorylation. In both cases, membrane-to-cortex attachment is dramatically reduced. Thus, our results suggest that SPAK inhibition differentially coordinates cotransporter and cytoskeleton-induced forces, to impact glioblastoma migration depending on the extent of confinement.

The filamentous actin (F-actin) cytoskeleton is a composite material consisting of cortical actin and bundled F-actin stress fibers, which together mediate the mechanical behaviors of the cell, from cell division to cell migration. However, as mechanical forces are typically measured upon transmission to the extracellular matrix, the internal distribution of forces within the cytoskeleton is unknown. Likewise, how distinct F-actin architectures contribute to the generation and transmission of mechanical forces is unclear. Therefore, we have developed a molecular tension sensor that embeds into the F-actin cytoskeleton. Using this sensor, we measure tension within stress fibers and cortical actin, as the cell is subject to uniaxial stretch. We find that the mechanical response, as measured by FRET, depends on the direction of applied stretch relative to the cell’s axis of alignment. When the cell is aligned parallel to the direction of the stretch, stress fibers and cortical actin both accumulate tension. By contrast, when aligned perpendicular to the direction of stretch, stress fibers relax tension while the cortex accumulates tension, indicating mechanical anisotropy within the cytoskeleton. We further show that myosin inhibition regulates this anisotropy. Thus, the mechanical anisotropy of the cell and the coordination between distinct F-actin architectures vary and depend upon applied load.

The surface tension of living cells and tissues originates from the generation of nonequilibrium active stresses within the cell cytoskeleton. Here, using laser ablation, we generate gradients in the surface tension of cellular aggregates as models of simple tissues. These gradients of active surface stress drive large-scale and rapid toroidal motion. Subsequently, the motions spontaneously reverse as stresses reaccumulate and cells return to their original positions. Both forward and reverse motions resemble Marangoni flows in viscous fluids. However, the motions are faster than the timescales of viscoelastic relaxation and the surface tension gradient is proportional to mechanical strain at the surface. Further, due to active stress, both the surface tension gradient and surface strain are dependent upon the volume of the aggregate. These results indicate that surface tension can induce rapid and highly correlated elastic deformations in the maintenance of tissue shape and configuration.

We explore the relationship between the nonequilibrium generation of myosin-induced active stress within the F-actin cytoskeleton and the pressure-volume relationship of cellular aggregates as models of simple tissues. We find that due to active stress, aggregate surface tension depends upon its size. As a result, both pressure and cell number density depend on size and violate equilibrium assumptions. However, the relationship between them resembles an equilibrium equation of state with an effective temperature. This suggests that bulk and surface properties of aggregates balance to yield a constant average work performed by each cell on their environment in regulating tissue size. These results describe basic physical principles that govern the size of cell aggregates.

Cell-matrix interfacial energies and the energies of matrix deformations may be comparable on cellular length-scales, yet how capillary effects influence tis sue shape and motion are unknown. In this work, we induce wetting (spreading and migration) of cell aggregates, as models of active droplets onto adhesive substrates of varying elasticity and correlate the dynamics of wetting to the balance of interfacial tensions. Upon wetting rigid substrates, cell-substrate tension drives outward expansion of the monolayer. By contrast, upon wetting compliant substrates, cell substrate tension is attenuated and aggregate capillary forces contribute to internal pressures that drive expansion. Thus, we show by experiments, data-driven modeling and computational simulations that myosin-driven 'active elasto-capillary' effects enable adaptation of wetting mechanisms to substrate rigidity and introduce a novel, pressure-based mechanism for guiding collective cell motion.

The trade-off between the fuel consumption and drag coefficient makes the investigations of drag reduction of utmost importance. In this paper, the rear-end shape optimization of Ahmed body is performed. Before changing the geometry, to identify the suitable simulation method and validate it, the standard Ahmed body is simulated using k − ω shear stress transport (SST) and k -epsilon turbulence models. The slant angle, rear box angle, and rear box length as variables were optimized simultaneously. Optimizations conducted by genetic algorithm (GA) and particle swarm optimization (PSO) methods indicate a 26.3% decrease in the drag coefficient. To ensure the validity of the results, a numerical-experimental study is conducted on the optimized model. Thereafter, the velocity profiles and flow structure in the boundary layers of the original geometry were compared to those of the optimized geometry at different sections. The results indicate that there are points where the velocity profile in the boundary layer can exceed the free stream velocity and return to it again, an overlooked observation in the previous studies. In addition to the streamlines, to better understand the formation of three-dimensional vortexes, the Q -criterion factor is computed and illustrated.

Kidney stones are stiff deposit minerals formed in the kidneys. In patients with kidney stones disease, double-J stents are used to increase the openness of the ureter in case of blockage by the kidney stones. The stent surfaces are normally smooth with symmetric friction along the longitudinal axis. In this work, we show that a modified double-J stent with asymmetric friction surface facilitates passage of stone fragments after extracorporeal shock wave lithotripsy or trans ureteral lithoclast. To examine the effect of asymmetric friction on the stone passing efficiency, finite element simulations were conducted. Simulation results revealed that at excitation vibration frequency of 0.15 Hz the stone unidirectionally moves along the stent at an average speed of 0.03 cm/s which is a significant increase compared to the clinical reports. Practically, the asymmetric friction can be made by laser micro-engraving techniques such as the same method in CD writing.

In liquid droplets, the balance of interfacial energies and substrate elasticity determines the shape of the droplet and the dynamics of wetting. In living cells, interfacial energies are not constant, but adapt to the mechanics of their environment. As a result, the forces driving the dynamics of wetting for cells and tissues are unclear and may be context specific. In this work, using a combination of experimental measurements and modeling, we show the surface tension of cell aggregates, as models of active liquid droplets, depends upon the size of the aggregate and the magnitude of applied load, which alters the wetting dynamics. Upon wetting rigid substrates, traction stresses are elevated at the boundary, and tension drives forward motion. By contrast, upon wetting compliant substrates, traction forces are attenuated, yet wetting occurs at a comparable rate. In this case, capillary forces at the contact line are elevated and aggregate surface tension contributes to strong outward, pressure-driven cellular flows. Thus, cell aggregates adapt to the mechanics of their environments, using pressure and traction as compensatory mechanisms to drive robust wetting.

Frontal vehicle crashes have been a leading cause of spinal injuries in recent years. Reconstruction of frontal crashes using computational models and spinal load analysis helps us understand the patterns of injury and load propagation during frontal crashes. By reconstructing a real crash test and using a viscoelastic crash dummy model, spinal injury patterns were analyzed. The results indicated that a moderate crash with an impact speed of 56 km/h leads to injuries in L1-L2 and L5-S1 levels (L for lumbar and S for sacral vertebrae). The largest spinal loads and injuries were mainly observed immediately after the airbag deployment when the peak of the crash acceleration transpires. Also, the effects of impulse magnitude on the spinal loads and head injury criterion (HIC) showed that HIC is more sensitive than compressive forces to the magnitude of impulse. Moreover, the effects of disc preconditioning as a major factor in the risk of injury was evaluated. The results demonstrate that as the lumbar spine is subjected to a longer preloading, it will be more vulnerable to injury; preconditioning of the discs more adversely affected the risk of injury than a 10% increase in the crash impulse. Overall the results highlight the importance of spinal injury prevention in frontal crashes.

Whole-body vibration (WBV) has been identified as one of the serious risk factors leading to spinal disorders, particularly in professional drivers. Although the influential factors in this area have been investigated epidemiologically, finite element (FE) modeling can efficiently help us better understand the problem. In this study, a modified HYBRID III dummy FE model which was enhanced by detailed viscoelastic discs in the lumbar region was utilized to simulate the effect of WBV on lumbar spine loads. Spinal responses to the vertical sinusoidal vibrations of a generic seat were obtained and spinal injury risk factors were calculated. Effects of variation of excitation frequencies, three different seatback inclinations and four pre-defined occupant postures on the spinal loads were investigated as influential variables. Results showed that under sinusoidal loading with a frequency of 5 Hz and in a typical sitting configuration, disc forces remained in a safe range (<1700 N) for short term. Collagen Fibers strain (<0.3%) and intradiscal pressure (<1.15 MPa) also indicated that the spinal loads were in a safe range. Additionally, calculating the risk factor according to ISO 2631-5 (about R = 0.8) confirmed the low probability of an adverse health effect due to WBV in long term. Frequency-domain analysis showed the resonance frequency to be at f = 6.27 Hz. Although according to ISO/CD 2631-5 standard, the occupant experienced the highest risk of injury at f = 7 Hz, it was found that spinal compression load at f = 6 Hz was 7.7% higher than the compression load at f = 7 Hz. Seatback oriented at 75° exhibited the highest risk of injury, nevertheless, maximum von-Mises stress in disc annulus was observed at 70°. In the evaluation of occupant posture, lordotic and slouching postures were compared and the latter exhibited higher stress ranges resulting in higher injury risk factor. Results of the model demonstrated its aptness to predict the spinal disc injuries in response to various vibrational loading and boundary conditions.

The dummies currently used for predicting vehicle occupant response during frontal crashes or whole-body vibration provide insufficient information about spinal loads. Although they aptly approximate upper-body rotations in different loading scenarios, they overlook spinal loads, which are crucial to injury assessment. This paper aims to develop a modified dummy finite element (FE) model with a detailed viscoelastic lumbar spine. This model has been developed and validated against in-vitro and in-silico data under different loading conditions, and its predicted ranges of motion (RoM) and intradiscal pressure (IDP) maintain close correspondence with the in-vitro data. The dominant frequency of the model was f = 8.92 Hz, which was close to previous results. In the relaxation test, a force reduction of up to 21% was obtained, showing high agreement in force relaxation during the in-vitro test. The FE lumbar spine model was placed in the HYBRID III test dummy and aligned in a seated position based on available MRI data. Under two impulsive acceleration loadings in flexion and lateral directions with a peak acceleration of 60 m/s2, flexion responses of the modified and original dummies were close (RoMs of 29.1° and 29.6°, respectively), though not in lateral bending (RoMs of 34.1° and 15.6°, respectively), where the modified dummy was more flexible than the original. By reconstructing a real frontal crash, it was found that the modified dummy provided a 10% reduction in the Head Injury Criterion (HIC). Other than the more realistic behavior of this modified dummy, its capability of approximating lumbar loads and risk of lumbar spine injuries in vehicle crashes or whole-body vibration is of great importance.

Biological applications of AFM in the liquid medium make the behavior of probe in the liquid medium very important to investigate. This study analyzes the effect of hysteresis and probe mass on the dynamics of AFM rectangular and dagger micro cantilevers (MC) in the liquid medium. To this end, the MCS theory was used for modeling the MC. The model considered the changes in the cross section and a zinc oxide piezoelectric layer between two electrode layers. The beam type of elements was selected and modeling was based on the finite element method (FEM) on the basis of Euler-Bernoulli beam theory. Fluid and the effects of its forces change the vibration behavior of the system. Simplified models have been proposed and used to implement the relationships. Several types of fluid were examined to determine the effect of fluid type on the frequency and time delay. Hysteresis effect causes a phase delay in the time response and a slight increase in the vibration amplitude in the liquid and the air media. The phase difference depends on the type of the medium in which it is placed; the more viscous and dense is the medium, the less the hysteresis effect will be.