Cellular orientational fluctuations, rotational diffusion and nematic order under periodic driving.

The ability of living cells to sense the physical properties of their microenvironment and to respond to dynamic forces acting on them plays a central role in regulating their structure, function and fate. Of particular importance is the cellular sensitivity and response to periodic driving forces in noisy environments, encountered in vital physiological conditions such as heart beating, blood vessel pulsation and breathing. Here, we first test and validate two predictions of a mean-field theory of cellular reorientation under periodic driving, which combines the minimization of cellular anisotropic elastic energy with active remodeling forces.

Cellular contractile forces are nonmechanosensitive.

Cells' ability to apply contractile forces to their environment and to sense its mechanical properties (e.g., rigidity) are among their most fundamental features.

Tissue-Level Mechanosensitivity: Predicting and Controlling the Orientation of 3D Vascular Networks.

Understanding the mechanosensitivity of tissues is a fundamentally important problem having far-reaching implications for tissue engineering. Here we study vascular networks formed by a coculture of fibroblasts and endothelial cells embedded in three-dimensional biomaterials experiencing external, physiologically relevant forces. We show that cyclic stretching of the biomaterial orients the newly formed network perpendicular to the stretching direction, independent of the geometric aspect ratio of the biomaterial's sample.

Conformational states during vinculin unlocking differentially regulate focal adhesion properties.

Focal adhesions (FAs) are multi-protein complexes that connect the actin cytoskeleton to the extracellular matrix, via integrin receptors. The growth, stability and adhesive functionality of these structures are tightly regulated by mechanical stress, yet, despite the extensive characterization of the integrin adhesome, the detailed molecular mechanisms underlying FA mechanosensitivity are still unclear. Besides talin, another key candidate for regulating FA-associated mechanosensing, is vinculin, a prominent FA component, which possesses either closed ("auto-inhibited") or open ("active") conformation.

The inner workings of stress fibers - from contractile machinery to focal adhesions and back.

Ventral stress fibers and focal adhesions are physically coupled structures that play key roles in cellular mechanics and force sensing. The tight functional interdependence between the two is manifested not only by their apparent proximity but also by the fact that ventral stress fibers and focal adhesions are simultaneously diminished upon actomyosin relaxation, and grow when subjected to external stretching. However, whereas the apparent co-regulation of the two structures is well-documented, the underlying mechanisms remains poorly understood.

Mechanical interplay between invadopodia and the nucleus in cultured cancer cells.

Invadopodia are actin-rich membrane protrusions through which cells adhere to the extracellular matrix and degrade it. In this study, we explored the mechanical interactions of invadopodia in melanoma cells, using a combination of correlative light and electron microscopy. We show here that the core actin bundle of most invadopodia interacts with integrin-containing matrix adhesions at its basal end, extends through a microtubule-rich cytoplasm, and at its apical end, interacts with the nuclear envelope and indents it.

Cell reorientation under cyclic stretching.

Mechanical cues from the extracellular microenvironment play a central role in regulating the structure, function and fate of living cells. Nevertheless, the precise nature of the mechanisms and processes underlying this crucial cellular mechanosensitivity remains a fundamental open problem. Here we provide a novel framework for addressing cellular sensitivity and response to external forces by experimentally and theoretically studying one of its most striking manifestations--cell reorientation to a uniform angle in response to cyclic stretching of the underlying substrate.

Acquisition of inertia by a moving crack.

We experimentally investigate the dynamics of "simple" tensile cracks. Within an effectively infinite medium, a crack's dynamics perfectly correspond to inertialess behavior predicted by linear elastic fracture mechanics. Once a crack interacts with waves that it generated at earlier times, this description breaks down.

The near-tip fields of fast cracks.

In a stressed body, crack propagation is the main vehicle for material failure. Cracks create large stress amplification at their tips, leading to large material deformation. The material response within this highly deformed region will determine its mode of failure.

Weakly nonlinear theory of dynamic fracture.

The common approach to crack dynamics, linear elastic fracture mechanics, assumes infinitesimal strains and predicts a r(-1/2) strain divergence at a crack tip. We extend this framework by deriving a weakly nonlinear fracture mechanics theory incorporating the leading nonlinear elastic corrections that must occur at high strains. This yields strain contributions "more divergent" than r(-1/2) at a finite distance from the tip and logarithmic corrections to the parabolic crack tip opening displacement.

Breakdown of linear elastic fracture mechanics near the tip of a rapid crack.

We present high resolution measurements of the displacement and strain fields near the tip of a dynamic (mode I) crack. The experiments are performed on polyacrylamide gels, brittle elastomers whose fracture dynamics mirror those of typical brittle amorphous materials. Over a wide range of propagation velocities (0.

Oscillations in rapid fracture.

Experiments of pure tensile fracture in thin brittle gels reveal a new dynamic oscillatory instability whose onset occurs at a critical velocity, VC=0.87CS, where CS is the shear wave speed. Until VC, crack dynamics are well described by linear elastic fracture mechanics (LEFM).