Muscle-Like Behaviour of Non-Muscle Cells and Real-Time Single Cell Response to Stiffness

Abstract

As part of their physiological functions, most cells need to respond to mechanical stimuli such as deformations, forces, and stiffness of the extracellular matrix. In particular, cells cultured on elastic substrates with a rigidity gradient align their shape, their cytoskeletal structures and their traction forces along the direction of highest stiffness.In order to identify the role of actomyosin-based contractility in rigidity sensing, we developed a single cell technique allowing us to measure the traction force as well as the speed of shortening of isolated cells deflecting microplates (i.e. springs) of variable stiffness. We will show that the mechanical power (energy per unit time) invested by the cell to bend the microplates was adapted to stiffness, and reflected the force-dependent kinetics of myosin binding to actin (Hill law of muscle contraction)1. We will also present a unique force-measurement protocol allowing us to change the effective stiffness felt by a single cell in real time (∼0.1 second). This technique revealed that cell contractility was instantaneously adapted to the change in stiffness2.Such an instantaneous response could hardly be explained by chemical transduction pathways. It would rather suggest that early cell response to stiffness could be purely mechanical in nature. This mechanical adaptation may translate anisotropy in substrate rigidity into anisotropy in cytoskeletal tension, and could thus coordinate local activity of adhesion complexes and guide cell migration along rigidity gradients.[1] Mitrosslis et al., “Single-cell response to stiffness exhibits muscle-like behavior”, PNAS, 106, 43, 2009.[2] Mitrosslis et al., “Real-time single-cell response to stiffness”, PNAS, 107, 38, 2010.