We address three problems that limit the use of the atomic force microscope when measuring elastic moduli of soft materials at microscopic scales. The first concerns the use of sharp cantilever tips, which typically induce local strains that far exceed the linear material regime. We show that this problem can be alleviated by using microspheres as probes, and we establish the criteria for their use. The second relates to the common use of the Hertz contact mechanics model, which leads to significant errors when applied to thin samples. We develop novel, simple to use corrections to apply for such cases. Samples that are either bonded or not bonded to a rigid substrate are considered. The third problem concerns the difficulty in establishing when contact occurs on a soft material. We obtain error estimates for the elastic modulus resulting from such uncertainty and discuss the sensitivity of the estimation methods to error in contact point. The theoretical and experimental results are compared to macroscopic measurements on poly(vinyl-alcohol) gels.

The elastic behavior of the 3D extracellular matrix determines the relative polarization of intracellular signaling and whether cells migrate using lamellipodia or lobopodia.

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The conventional theory about the snail shell shape of the mammalian cochlea is that it evolved essentially and perhaps solely to conserve space inside the skull. Recently, a theory proposed that the spiral's graded curvature enhances the cochlea's mechanical response to low frequencies. This article provides a multispecies analysis of cochlear shape to test this theory and demonstrates that the ratio of the radii of curvature from the outermost and innermost turns of the cochlear spiral is a significant cochlear feature that correlates strongly with low-frequency hearing limits. The ratio, which is a measure of curvature gradient, is a reflection of the ability of cochlear curvature to focus acoustic energy at the outer wall of the cochlear canal as the wave propagates toward the apex of the cochlea.inner ear ͉ function ͉ mammalian evolution ͉ spiral I t is often thought that mammalian cochleae are coiled to pack a longer organ into a small space inside the skull and that the cochlear coil increases the efficiency of blood and nerve supply through a central shaft (1). Although these spatial advantages of a coiled cochlea have been generally accepted, understanding the effect of shape on hearing itself has been a challenge.Cochlear coiling is absent in reptiles, birds, and monotreme mammals, and it appears to have originated in the marsupial and placental mammal lines (2). Coiling allowed the cochlea to become longer, increasing the potential octave range, whereas uncoiled cochleae have been associated with relatively limited hearing ranges. Earlier studies suggested that the evolution of coiling enhanced high-frequency hearing (3). This suggestion, however, is not wholly satisfactory for several reasons. Above all, increased hearing ranges extended both high-frequency and low-frequency (LF) hearing abilities in mammals compared with birds and reptiles and improved sensitivities compared with even LF specialist fishes (4). Further, the highest-frequency waves are resolved near the base (entrance) before they propagate far enough into the spiral to ''feel'' the cochlear curvature; it is the lowest-frequency waves that propagate along the cochlea's coils.Earlier work on land mammal ear anatomy (5) found a strong correlation between the LF hearing limit of each species and the product of basilar membrane length and number of spiral turns, but did not adduce a mechanistic explanation for this relationship. Other data suggested also that longitudinal curvature of the cochlear duct generates radial fluid pressure gradients (6) and enhances radial movement of hair cells (1, 7).Recently, a new theory proposed that the cochlea's graded curvature actually enhances LF hearing (8), similar to a whispering gallery in which sounds cling to the concave surface of the lateral wall (9). The cochlear spiral shape redistributes wave energy toward the outer wall, particularly along its innermost, tightest, apical turn, and thereby enhances sensitivity to lowerfrequency sounds.In this article, we test this theory morphometrically. W...

Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-adhesive environment migrate in the direction of a very large ‘leader bleb.’ Eps8 bundling activity promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under non-adhesive confinement.DOI: http://dx.doi.org/10.7554/eLife.08314.001

Direct interstitial infusion is a technique capable of delivering agents over both small and large dimensions of brain tissue. However, at a sufficiently high volumetric inflow rate, backflow along the catheter shaft may occur and compromise delivery. A scaling relationship for the finite backflow distance along this catheter in pure gray matter (x(m)) has been determined from a mathematical model based on Stokes flow, Darcy flow in porous media, and elastic deformation of the brain tissue: x(m) = constant Q(o)(3)R(4)r(c)(4)G(-3)mu(-1) 1/5 [corrected] = volumetric inflow rate, R = tissue hydraulic resistance, r(c) = catheter radius, G = shear modulus, and mu = viscosity). This implies that backflow is minimized by the use of small diameter catheters and that a fixed (minimal) backflow distance may be maintained by offsetting an increase in flow rate with a similar decrease in catheter radius. Generally, backflow is avoided in rat gray matter with a 32-gauge catheter operating below 0.5 microliter/min. An extension of the scaling relationship to include brain size in the resistance term leads to the finding that absolute backflow distance obtained with a given catheter and inflow rate is weakly affected by the depth of catheter tip placement and, thus, brain size. Finally, an extension of the model to describe catheter passage through a white matter layer before terminating in the gray has been shown to account for observed percentages of albumin in the corpus callosum after a 4-microliter infusion of the compound to rat striatum over a range of volumetric inflow rates.

The motion of a sphere in the presence of a fluid-fluid interface is studied. First, a solution is derived for a point force near a plane interface. Then the solution is extended to include the higher-order terms which are required to describe the motion of a solid sphere. Singularities of higher orders at the centre of the sphere are obtained by using the method of reflexions. For a fluid-fluid interface with an arbitrary viscosity ratio, the drag force and the hydrodynamic torque are calculated for the special cases of motion of a sphere perpendicular and parallel to the interface. In addition, the rotational motion of a sphere is also investigated.

Actomyosin stress fibers, one of the main components of the cell's cytoskeleton, provide mechanical stability to adherent cells by applying and transmitting tensile forces onto the extracellular matrix (ECM) at the sites of cell-ECM adhesion. While it is widely accepted that changes in spatial and temporal distribution of stress fibers affect the cell's mechanical properties, there is no quantitative knowledge on how stress fiber amount and organization directly modulate cell stiffness. We address this key open question by combining atomic force microscopy with simultaneous fluorescence imaging of living cells, and combine for the first time reliable quantitative parameters obtained from both techniques. We show that the amount of myosin and (to a lesser extent) actin assembled in stress fibers directly modulates cell stiffness in adherent mouse fibroblasts (NIH3T3). In addition, the spatial distribution of stress fibers has a second-order modulatory effect. In particular, the presence of either fibers located in the cell periphery, aligned fibers or thicker fibers gives rise to reinforced cell stiffness. Our results provide basic and significant information that will help design optimal protocols to regulate the mechanical properties of adherent cells via pharmacological interventions that alter stress fiber assemElectronic supplementary material The online version of this article (doi:10.1007/s10237-015-0706-9) contains supplementary material, which is available to authorized users.