We used a novel uniaxial stretching rheometer to measure the creep function J(t) of an isolated living cell. We show, for the first time at the scale of the whole cell, that J(t) behaves as a power-law J(t) = At(alpha). For N = 43 mice myoblasts (C2-7), we find alpha = 0.24 +/- 0.01 and A = (2.4 +/- 0.3) 10(-3) Pa(-1) s(-alpha). Using Laplace Transforms, we compare A and alpha to the parameters G(0) and beta of the complex modulus G*(omega) = G(0)omega(beta) measured by other authors using magnetic twisting cytometry and atomic force microscopy. Excellent agreement between A and G(0) on the one hand, and between alpha and beta on the other hand, indicated that the power-law is an intrinsic feature of cell mechanics and not the signature of a particular technique. Moreover, the agreement between measurements at very different size scales, going from a few tens of nanometers to the scale of the whole cell, suggests that self-similarity could be a central feature of cell mechanical structure. Finally, we show that the power-law behavior could explain previous results first interpreted as instantaneous elasticity. Thus, we think that the living cell must definitely be thought of as a material with a large and continuous distribution of relaxation time constants which cannot be described by models with a finite number of springs and dash-pots.

Living cells sense the rigidity of their environment and adapt their activity to it. In particular, cells cultured on elastic substrates align their shape and their traction forces along the direction of highest stiffness and preferably migrate towards stiffer regions. Although numerous studies investigated the role of adhesion complexes in rigidity sensing, less is known about the specific contribution of acto-myosin based contractility. Here we used a custom-made single-cell technique to measure the traction force as well as the speed of shortening of isolated myoblasts deflecting microplates of variable stiffness. The rate of force generation increased with increasing stiffness and followed a Hill force-velocity relationship. Hence, cell response to stiffness was similar to muscle adaptation to load, reflecting the force-dependent kinetics of myosin binding to actin. These results reveal an unexpected mechanism of rigidity sensing, whereby the contractile acto-myosin units themselves can act as sensors. This mechanism 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.mechanosensing | adaptation to load | cell migration | cell spreading | cell mechanics A s part of their normal physiological functions, most cells in the organism need to respond to mechanical stimuli such as deformations, forces, and the geometry and stiffness of the extracellular matrix (1, 2). Aberrant mechanical responsiveness is often associated with severe diseases, including cardiovascular disorders, asthma, fibrotic diseases, or cancer metastasis.Since the early 1980s, several techniques have been developed to characterize the forces generated by living cells (3-5) and to investigate the effect of the mechanical properties of twodimensional (2D) substrates (6-8). It was shown that cells are able to sense and respond to the rigidity of their surroundings. For instance, cells cultured on elastic substrates with a rigidity gradient preferably locomote towards stiffer regions and align their shape, their cytoskeletal structures, and their traction forces along the direction of highest stiffness (9-11). Moreover, it has been demonstrated that matrix rigidity could direct stem cells' lineage specification (12).It is generally assumed that rigidity sensing is based on mechanochemical signal-transduction pathways. The search for the mechanosensing element has generated numerous plausible candidates (reviewed in ref.2). The most prominent of them is the focal adhesion complex (13,14). These molecular assemblies consist of numerous proteins that are associated with integrin adhesion receptors (15) and provide the pathway of force transmission from the cytoskeleton to the extracellular matrix (16). Adhesion of integrins to extracellular matrix proteins triggers the formation of focal adhesions, their connection to actin, and the contraction of the cytoskeleton by myosin II (17-19). On a soft substrat...