Contractile Fibers and Catch-Bond Clusters: a Biological Force Sensor?

Abstract

Catch bonds are cellular receptor-ligand pairs whose lifetime, counterintuitively, increases with increasing load. Although their existence was initially pure theoretical speculation, recent years have seen several experimental demonstrations of catch-bond behavior in biologically relevant and functional protein-protein bonds. Particularly notable among these established catch-bond formers is the integrin α5β1, the primary receptor for fibronectin and, as such, a crucial determinant for the characteristics of the mechanical coupling between cell and matrix. In this work, we explore the implications of single catch-bond characteristics for the behavior of a load-sharing cluster of such bonds: These clusters are shown to possess a regime of strengthening with increasing applied force, similar to the manner in which focal adhesions become selectively reinforced. Our results may shed new light on the fundamental processes that allow cells to sense and respond to the mechanical properties of their environment and in particular show how single focal adhesions may act, autonomously, as local rigidity sensors.

Role of catch bonds in actomyosin mechanics and cell mechanosensitivity

“…Such bonds are typically found on the membrane of leucocytes and bacteria [19] and act to strengthen the adhesion with a solid substrate in the presence of an external force. They may also play the role of rigidity sensors on the surface of adherent cells, through specific membrane receptors and notably the α 5 β 1 integrin [20]. Contrary to the conventional slip bonds whose detachment rate increases with force as described by Bell’s law [21], catch bonds are able to extend their lifetime under the application of a small to moderate force.…”

A discrete approach for modeling cell–matrix adhesions

“…Chan and Odde [7] investigated ECM rigidity sensing of filopodia via a stochastic model of the motorclutch force transmission system, where integrin molecules work as mechanical clutches linking F-actin to the substrate and mechanically resisting myosin-driven F-actin retrograde flow. More recently, Novikova et al [27] proposed an original mathematical model for stiffness-sensing at focal adhesions, based on the interplay of catch-bond dynamics in the integrin layer and intracellular force generation through contractile fibers. One of the main limitations of these approaches is the assumption that total force is equally transmitted to all the bonds, not considering the spatial distribution of the focal adhesions.…”

Cell Shape and Durotaxis Follow from Mechanical Cell-Substrate Reciprocity and Focal Adhesion Dynamics: A Unifying Mathematical Model

“…Focal adhesions: We model focal adhesions as clusters of catch-slip bonds, as proposed by Novikova and Storm [41]. This model is based on experimental data of one single α5 − β1 integrin, of which the degradation rate of bound integrins decreases with force.…”

“…With a hybrid cell and focal adhesion model we propose a focal adhesion mechanism that unifyingly explains three ECM stiffness-dependent cell behaviors: cell spreading, cell elongation, and durotaxis. The model is based on the following assumptions: (1) focal adhesions are discrete clusters of integrin-ECM bonds; (2) new bonds are added to the FAs at a constant rate; (3) the unbinding rate is suppressed by the tension in the FA, which is due to pulling of stress fibers [41]; (4) on soft ECMs it takes more time for the tension in the FA to build up to its maximum value, than on stiff ECMs [42]; therefore, on average, the unbinding rate in FAs is higher on soft ECMs than on stiff ECMs. (5) As a result, FAs grow larger on stiff ECMs than on softer ECMs; (6) thus the FAs detach less easily from the ECM on stiff matrices than on softer ones.…”