Mechanical forces play a major role in the regulation of cell adhesion and cytoskeletal organization. In order to explore the molecular mechanism underlying this regulation, we have investigated the relationship between local force applied by the cell to the substrate and the assembly of focal adhesions. A novel approach was developed for real-time, high-resolution measurements of forces applied by cells at single adhesion sites. This method combines micropatterning of elastomer substrates and fluorescence imaging of focal adhesions in live cells expressing GFP-tagged vinculin. Local forces are correlated with the orientation, total fluorescence intensity and area of the focal adhesions, indicating a constant stress of 5.5 +/- 2 nNmicrom(-2). The dynamics of the force-dependent modulation of focal adhesions were characterized by blocking actomyosin contractility and were found to be on a time scale of seconds. The results put clear constraints on the possible molecular mechanisms for the mechanosensory response of focal adhesions to applied force.

The shape and differentiation of human mesenchymal stem cells is especially sensitive to the rigidity of their environment; the physical mechanisms involved are unknown. A theoretical model and experiments demonstrate here that the polarization/alignment of stress-fibers within stem cells is a non-monotonic function of matrix rigidity. We treat the cell as an active elastic inclusion in a surrounding matrix whose polarizability, unlike dead matter, depends on the feedback of cellular forces that develop in response to matrix stresses. The theory correctly predicts the monotonic increase of the cellular forces with the matrix rigidity and the alignment of stress-fibers parallel to the long axis of cells. We show that the anisotropy of this alignment depends non-monotonically on matrix rigidity and demonstrate it experimentally by quantifying the orientational distribution of stress-fibers in stem cells. These findings offer a first physical insight for the dependence of stem cell differentiation on tissue elasticity.

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One of the most unique physical features of cell adhesion to external surfaces is the active generation of mechanical force at the cell-material interface. This includes pulling forces generated by contractile polymer bundles and networks, and pushing forces generated by the polymerization of polymer networks. These forces are transmitted to the substrate mainly by focal adhesions, which are large, yet highly dynamic adhesion clusters. Tissue cells use these forces to sense the physical properties of their environment and to communicate with each other. The effect of forces is intricately linked to the material properties of cells and their physical environment. Here a review is given of recent progress in our understanding of the role of forces in cell adhesion from the viewpoint of theoretical soft matter physics and in close relation to the relevant experiments.Comment: review, 60 pages, 25 figure

We develop a microscopic-level formulation for the curvature elasticity of monolayer and bilayer systems of typical surfactant molecules. It is argued that both the bending and saddle-splay force constants k and k̄ are determined primarily by the conformational entropy of the flexible hydrocarbon chain rather than by the electrostatic interactions associated with hydrophilic head groups. A priori estimates of the chain contributions are made for the first time, without the use of any adjustable parameters. Both k and k̄ are shown to be calculable wholly from the conformational statistics describing the planar film. In particular, these constants are expressed in terms of the derivatives and moments of the lateral pressure profile characterizing chain packing in the unbent layers. By considering the dependence of the curvature elasticity on chain length, area per molecule, and composition in mixed films, we are able to account for the order-of-magnitude variations in k observed in a variety of different surfactant systems. The replacement of long chain molecules by short ones is shown to be especially efficient in lowering the bending energy from 10’s of kBT to kBT. The effect of ‘‘free’’ vs ‘‘blocked’’ exchange are also presented and contrasted with the case of fixed area-per-molecule bending deformation. Finally, monolayer vs bilayer results are compared and the calculated signs and magnitudes of k and k̄ are discussed in the context of planar bilayer stability.