Tug-of-war in motility assay experiments

The dynamics of two groups of molecular motors pulling in opposite directions on a rigid filament is studied theoretically. To this end we first consider the behavior of one set of motors pulling in a single direction against an external force using a new mean-field approach. Based on these results we analyze a similar setup with two sets of motors pulling in opposite directions in a tug-of-war in the presence of an external force. In both cases we find that the interplay of fluid friction and protein friction leads to a complex phase diagram where the force-velocity relations can exhibit regions of bistability and spontaneous symmetry breaking. Finally, motivated by recent work, we turn to the case of motility assay experiments where motors bound to a surface push on a bundle of filaments. We find that, depending on the absence or the presence of a bistability in the force-velocity curve at zero force, the bundle exhibits anomalous or biased diffusion on long-time and large-length scales

Structure formation in active networks

Structure formation and constant reorganization of the actin cytoskeleton are key requirements for the function of living cells. Here we show that a minimal reconstituted system consisting of actin filaments, crosslinking molecules and molecular-motor filaments exhibits a generic mechanism of structure formation, characterized by a broad distribution of cluster sizes. We demonstrate that the growth of the structures depends on the intricate balance between crosslinker-induced stabilization and simultaneous destabilization by molecular motors, a mechanism analogous to nucleation and growth in passive systems. We also show that the intricate interplay between force generation, coarsening and connectivity is responsible for the highly dynamic process of structure formation in this heterogeneous active gel, and that these competing mechanisms result in anomalous transport, reminiscent of intracellular dynamics

Molecular motors robustly drive active gels to a critically connected state

Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

Collective dynamics of active cytoskeletal networks

Self organization mechanisms are essential for the cytoskeleton to adapt to the requirements of living cells. They rely on the intricate interplay of cytoskeletal filaments, crosslinking proteins and molecular motors. Here we present an in vitro minimal model system consisting of actin filaments, fascin and myosin-II filaments exhibiting pulsative collective long range dynamics. The reorganizations in the highly dynamic steady state of the active gel are characterized by alternating periods of runs and stalls resulting in a superdiffusive dynamics of the network's constituents. They are dominated by the complex competition of crosslinking molecules and motor filaments in the network: Collective dynamics are only observed if the relative strength of the binding of myosin-II filaments to the actin network allows exerting high enough forces to unbind actin/fascin crosslinks. The feedback between structure formation and dynamics can be resolved by combining these experiments with phenomenological simulations based on simple interaction rules

Actomyosin-Dependent Cortical Dynamics Contributes to the Prophase Force-Balance in the Early Drosophila Embryo

embryo mitotic spindle during prophase depends upon a balance of outward forces generated by cortical dynein and inward forces generated by kinesin-14 and nuclear elasticity. Myosin II is known to contribute to the dynamics of the cell cortex but how this influences the prophase force-balance is unclear. mutants displaying abnormally small actin caps but normal prophase spindle length in late prophase, myosin II inhibition produced very short spindles.These results suggest that two complementary outward forces are exerted on the prophase spindle by the overlying cortex. Specifically, dynein localized on the mechanically firm actin caps and the actomyosin-driven contraction of the deformable soft patches of the actin cortex, cooperate to pull astral microtubules outward. Thus, myosin II controls the size and dynamic properties of the actin-based cortex to influence the spacing of the poles of the underlying spindle during prophase

River histories : A thematic review

Peer reviewe

Reconstitution of the transition from lamellipodium to filopodium in a membrane-free system

The cellular cytoskeleton is a complex dynamical network that constantly remodels as cells divide and move. This reorganization process occurs not only at the cell membrane, but also in the cell interior (bulk). During locomotion, regulated actin assembly near the plasma membrane produces lamellipodia and filopodia. Therefore, most in vitro experiments explore phenomena taking place in the vicinity of a surface. To understand how the molecular machinery of a cell self-organizes in a more general way, we studied bulk polymerization of actin in the presence of actin-related protein 2/3 complex and a nucleation promoting factor as a model for actin assembly in the cell interior separate from membranes. Bulk polymerization of actin in the presence of the verprolin homology, cofilin homology, and acidic region, domain of Wiskott-Aldrich syndrome protein, and actin-related protein 2/3 complex results in spontaneous formation of diffuse aster-like structures. In the presence of fascin these asters transition into stars with bundles of actin filaments growing from the surface, similar to star-like structures recently observed in vivo. The transition from asters to stars depends on the ratio [fascin]/[G actin]. The polarity of the actin filaments during the transition is preserved, as in the transition from lamellipodia to filopodia. Capping protein inhibits star formation. Based on these experiments and kinetic Monte Carlo simulations, we propose a model for the spontaneous self-assembly of asters and their transition into stars. This mechanism may apply to the transition from lamellipodia to filopodia in vivo