Force percolation of contractile active gels

Abstract

Living systems provide a paradigmatic example of active soft matter. Cells and tissues comprise viscoelastic materials that exert forces and can actively change shape. This strikingly autonomous behavior is powered by the cytoskeleton, an active gel of semiflexible filaments, crosslinks, and molecular motors inside cells. Although individual motors are only a few nm in size and exert minute forces of a few pN, cells spatially integrate the activity of an ensemble of motors to produce larger contractile forces (∼nN and greater) on cellular, tissue, and organismal length scales. Here we review experimental and theoretical studies on contractile active gels composed of actin filaments and myosin motors. Unlike other active soft matter systems, which tend to form ordered patterns, actin-myosin systems exhibit a generic tendency to contract. Experimental studies of reconstituted actin-myosin model systems have long suggested that a mechanical interplay between motor activity and the network's connectivity governs this contractile behavior. Recent theoretical models indicate that this interplay can be understood in terms of percolation models, extended to include effects of motor activity on the network connectivity. Based on concepts from percolation theory, we propose a state diagram that unites a large body of experimental observations. This framework provides valuable insights into the mechanisms that drive cellular shape changes and also provides design principles for synthetic active materials.

Myosin-driven fragmentation of actin filaments triggers contraction of a disordered actin network

“…These clusters often combined, slightly increasing the overall cluster size (32). This indicated that myosin minifilaments not only generate contractile force but also cross-link actin filaments, as predicted by theoretical studies (13) (15). With increasing anillin concentration (0.36 M), myosin activity broke the passive cross-linked actin network into multiple disjointed medium-size clusters with a mean maximum cluster size of 100 to 1,000 m 2 (hereafter referred to as medium clusters; Fig.…”

“…1 B and Fig. 1 C, open square, and see Movie 5 in Supporting Material) (15). Further, we controlled the internal stresses by varying the amount of myosin II in the presence of fixed concentrations of G-actin and anillin (3 M and 0.36 M, respectively), and observed the selforganizing process of the disordered actin network.…”

“…An excess of cross-linking proteins that bundles actin filaments impedes myosin-driven actin sliding by mechanical constraints. The resultant networks are mechanically stable, whereas myosin-driven contractile stresses are maintained across it (15). Contraction of the stable network by remodeling an existing actin network requires a trigger that can remove the impediment caused by a cross-linker.…”

Tissue rheology in embryonic organization

“…Conversely, morphogen signalling, and specifically the Wnt/PCP pathway, was proposed to increase tissue rigidity by promoting junctional stability and cell density Petridou et al, 2019). vertex Voronoi, self-propelled, percolation theory) will be needed to elucidate the molecular and cellular control mechanisms determining tissue rheology (Szabó et al, 2006;Garcia et al, 2015;Alt et al, 2017;Alvarado et al, 2017). Generally, to attribute the regulation of tissue rheological properties to certain structural or cellular features is still challenging, as these features are often interdependent, making functional assays rather difficult to interpret.…”

“…Systematic analysis of such features alone and in combination, and the development of theoretical models from statistical physics to, e.g., simulate network rigidity (i.e. vertex Voronoi, self-propelled, percolation theory) will be needed to elucidate the molecular and cellular control mechanisms determining tissue rheology (Szabó et al, 2006;Garcia et al, 2015;Alt et al, 2017;Alvarado et al, 2017). Furthermore, different cell and tissue types might be differently regulated in terms of their rheological properties, and it thus will be important to consider cell fate specification and differentiation factors when analysing the regulation of tissue rheology.…”