Differential cellular contractility as a mechanism for stiffness sensing

Carina Dunlop

doi:10.1088/1367-2630/ab210a

Abstract

The ability of cells to sense and respond to the mechanical properties of their environments is fundamental to a range of cellular behaviours, with substrate stiffness increasingly being found to be a key signalling factor. Although active contractility of the cytoskeleton is clearly necessary for stiffness sensing in cells, the physical mechanisms connecting contractility with mechanosensing and molecular conformational change are not well understood. Here we present a contractility-driven mechanism for linking changes in substrate stiffness with internal conformational changes. Cellular contractility is often assumed to imply an associated compressive strain. We show, however, that where the contractility is non-uniform, localized areas of internal stretch can be generated as stiffer substrates are encountered. This suggests a physical mechanism for the stretch-activation of mechanotransductive molecules on stiffer substrates. Importantly, the areas of internal stretch occur deep within the cell and not near the cellular perimeter, which region is more traditionally associated with stiffness sensing through e.g. focal adhesions. This supports recent experimental results on whole-cell mechanically-driven mechanotransduction. Considering cellular shape we show that aspect ratio acts as an additional control parameter, so that the onset of positive strain moves to higher stiffness values in elliptical cells.

Highlights

It is clear that the mechanical properties of cell environments play a crucial role in controlling and coordinating cell behaviours both individually and within multicellular tissues
It has been observed that substrate stiffness has a significant influence on phenotype across a range of cell types, for example, experiments have shown that stem cells can alter their differentiation target [1], cardiomyocytes de-differentiate and initiate proliferation [2], and fibroblasts change their DNA synthesis and undergo apoptosis [3] in response to changes in the stiffness they encounter
Na et al [16] have demonstrated that the speed of activation of Src molecules and the colocalisation of this activation with microtubule deformation implies a physical mechanism for transmitting force to internal stretch-activation molecules

Summary

Introduction

It is clear that the mechanical properties of cell environments play a crucial role in controlling and coordinating cell behaviours both individually and within multicellular tissues. The point of maximum strain is significantly set back from the cell periphery so that the region of stretching is not co-localised with the maximum mechanical activity and application of traction forces at the cell edges. Exploring further how the substrate elasticity affects the within-cell strain we plot in Fig. 2(a) the maximum positive radial strain (where the strain is purely negative the value is set to zero).

Results

Conclusion