Contractile units in disordered actomyosin bundles arise from F-actin buckling

Bundles of filaments and motors are central to contractility in cells. The classic example is striated muscle, where actomyosin contractility is mediated by highly organized sarcomeres which act as fundamental contractile units. However, many contractile bundles in vivo and in vitro lack sarcomeric organization. Here we propose a model for how contractility can arise in actomyosin bundles without sarcomeric organization and validate its predictions with experiments on a reconstituted system. In the model, internal stresses in frustrated arrangements of motors with diverse velocities cause filaments to buckle, leading to overall shortening. We describe the onset of buckling in the presence of stochastic actin-myosin detachment and predict that buckling-induced contraction occurs in an intermediate range of motor densities. We then calculate the size of the "contractile units" associated with this process. Consistent with these results, our reconstituted actomyosin bundles contract at relatively high motor density, and we observe buckling at the predicted length scale.Comment: 5 pages, 4 figures, Supporting text and movies attache

Myosin II-Mediated Focal Adhesion Maturation Is Tension Insensitive

Myosin II motors drive changes in focal adhesion morphology and composition in a “maturation process” that is crucial for regulating adhesion dynamics and signaling guiding cell adhesion, migration and fate. The underlying mechanisms of maturation, however, have been obscured by the intermingled effects of myosin II on lamellar actin architecture, dynamics and force transmission. Here, we show that focal adhesion growth rate stays constant even when cellular tension is reduced by 75%. Focal adhesion growth halts only when myosin stresses are sufficiently low to impair actin retrograde flow. Focal adhesion lifetime is reduced at low levels of cellular tension, but adhesion stability can be rescued at low levels of force by over-expression of α-actinin or constitutively active Dia1. Our work identifies a minimal myosin activity threshold that is necessary to drive lamellar actin retrograde flow is sufficient to permit focal adhesion elongation. Above this nominal threshold, myosin-mediated actin organization and dynamics regulate focal adhesion growth and stability in a force-insensitive fashion.</p

Requirements for contractility in disordered cytoskeletal bundles

Actomyosin contractility is essential for biological force generation, and is well understood in highly organized structures such as striated muscle. Additionally, actomyosin bundles devoid of this organization are known to contract both in vivo and in vitro, which cannot be described by standard muscle models. To narrow down the search for possible contraction mechanisms in these systems, we investigate their microscopic symmetries. We show that contractile behavior requires non-identical motors that generate large enough forces to probe the nonlinear elastic behavior of F-actin. This suggests a role for filament buckling in the contraction of these bundles, consistent with recent experimental results on reconstituted actomyosin bundles.Comment: 10 pages, 6 figures; text shortene

A cycling state that can lead to glassy dynamics in intracellular transport

Power-law dwell times have been observed for molecular motors in living cells, but the origins of these trapped states are not known. We introduce a minimal model of motors moving on a two-dimensional network of filaments, and simulations of its dynamics exhibit statistics comparable to those observed experimentally. Analysis of the model trajectories, as well as experimental particle tracking data, reveals a state in which motors cycle unproductively at junctions of three or more filaments. We formulate a master equation for these junction dynamics and show that the time required to escape from this vortex-like state can account for the power-law dwell times. We identify trends in the dynamics with the motor valency for further experimental validation. We demonstrate that these trends exist in individual trajectories of myosin II on an actin network. We discuss how cells could regulate intracellular transport and, in turn, biological function, by controlling their cytoskeletal network structures locally

Tunable structure and dynamics of active liquid crystals

Active materials are capable of converting free energy into directional motion, giving rise to notable dynamical phenomena. Developing a general understanding of their structure in relation to the underlying nonequilibrium physics would provide a route toward control of their dynamic behavior and pave the way for potential applications. The active system considered here consists of a quasi-two-dimensional sheet of short (1 mm) actin filaments driven by myosin II motors. By adopting a concerted theoretical and experimental strategy, new insights are gained into the nonequilibrium properties of active nematics over a wide range of internal activity levels. In particular, it is shown that topological defect interactions can be led to transition from attractive to repulsive as a function of initial defect separation and relative orientation. Furthermore, by examining the +1/2 defect morphology as a function of activity, we found that the apparent elastic properties of the system (the ratio of bend-to-splay elastic moduli) are altered considerably by increased activity, leading to an effectively lower bend elasticity. At high levels of activity, the topological defects that decorate the material exhibit a liquid-like structure and adopt preferred orientations depending on their topological charge. Together, these results suggest that it should be possible to tune internal stresses in active nematic systems with the goal of designing out-of-equilibrium structures with engineered dynamic responses