Stochastic dynamics of adhesion clusters under shared constant force and with rebinding

Single receptor-ligand bonds have finite lifetimes, so that biological systems can dynamically react to changes in their environment. In cell adhesion, adhesion bonds usually act cooperatively in adhesion clusters. Outside the cellular context, adhesion clusters can be probed quantitatively by attaching receptors and ligands to opposing surfaces. Here we present a detailed theoretical analysis of the stochastic dynamics of a cluster of parallel bonds under shared constant loading and with rebinding. Analytical solutions for the appropriate one-step master equation are presented for special cases, while the general case is treated with exact stochastic simulations. If the completely dissociated state is modeled as an absorbing boundary, mean cluster lifetime is finite and can be calculated exactly. We also present a detailed analysis of fluctuation effects and discuss various approximations to the full stochastic description.Comment: Revtex, 29 pages, 23 postscript figures included (some with reduced image quality

Bistability of cell-matrix adhesions resulting from non-linear receptor-ligand dynamics

Bistability is a major mechanism for cellular decision making and usually results from positive feedback in biochemical control systems. Here we show theoretically that bistability between unbound and bound states of adhesion clusters results from positive feedback mediated by structural rather than biochemical processes, namely by receptor-ligand dissociation and association dynamics which depend non-linearly on mechanical force and receptor-ligand separation. For small cell-matrix adhesions, we find rapid switching between unbound and bound states, which in the initial stages of adhesion allows the cell to explore its environment through many transient adhesions.Comment: Revtex, 3 pages, 3 postscript figures included, to appear in Biophysical Journal as Biophysical Lette

Focal adhesions as mechanosensors: the two-spring model

Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include

Focal adhesions as mechanosensors: the two-spring model

Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include

Noise-Induced Transition from Translational to Rotational Motion of Swarms

We consider a model of active Brownian agents interacting via a harmonic attractive potential in a two-dimensional system in the presence of noise. By numerical simulations, we show that this model possesses a noise-induced transition characterized by the breakdown of translational motion and the onset of swarm rotation as the noise intensity is increased. Statistical properties of swarm dynamics in the weak noise limit are further analytically investigated.Comment: 7 pages, 7 figure