Stress relaxation in F-actin solutions by severing

Networks of filamentous actin (F-actin) are important for the mechanics of most animal cells. These cytoskeletal networks are highly dynamic, with a variety of actin-associated proteins that control cross-linking, polymerization and force generation in the cytoskeleton. Inspired by recent rheological experiments on reconstituted solutions of dynamic actin filaments, we report a theoretical model that describes stress relaxation behavior of these solutions in the presence of severing proteins. We show that depending on the kinetic rates of assembly, disassembly, and severing, one can observe both length-dependent and length-independent relaxation behavior

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

Monte Carlo study of multiply crosslinked semiflexible polymer networks

We present a method to generate realistic, three-dimensional networks of crosslinked semiflexible polymers. The free energy of these networks is obtained from the force-extension characteristics of the individual polymers and their persistent directionality through the crosslinks. A Monte Carlo scheme is employed to obtain isotropic, homogeneous networks that minimize the free energy, and for which all of the relevant parameters can be varied: the persistence length, the contour length as well as the crosslinking length may be chosen at will. We also provide an initial survey of the mechanical properties of our networks subjected to shear strains, showing them to display the expected non-linear stiffening behavior. Also, a key role for non-affinity and its relation to order in the network is uncovered.Comment: 11 pages, revised figures, added extra information about the network

Contamination des poissons par les corps radio-actifs. Etude expérimentale sur le métabolisme du Ca45 insoluble (Note technique préliminaire)

Dumeste Marcel H., Gardel R. Contamination des poissons par les corps radio-actifs. Etude expérimentale sur le métabolisme du Ca45 insoluble. (Note technique et préliminaire). In: Bulletin de l'Académie Vétérinaire de France tome 111 n°7, 1958. pp. 371-378

Microrheology probes length scale dependent rheology

We exploit the power of microrheology to measure the viscoelasticity of entangled F-actin solutions at different length scales from 1 to 100 mu m over a wide frequency range. We compare the behavior of single probe-particle motion to that of the correlated motion of two particles. By varying the average length of the filaments, we identify fluctuations that dissipate diffusively over the filament length. These provide an important relaxation mechanism of the elasticity between 0.1 and 30 rad/sec

Local Cortical Tension by Myosin II Guides 3D Endothelial Cell Branching

SummaryA key feature of angiogenesis is directional control of endothelial cell (EC) morphogenesis and movement [1]. During angiogenic sprouting, endothelial “tip cells” directionally branch from existing vessels in response to biochemical cues such as VEGF or hypoxia and migrate and invade the surrounding extracellular matrix (ECM) in a process that requires ECM remodeling by matrix metalloproteases (MMPs) [2–4]. Tip EC branching is mediated by directional protrusion of subcellular pseudopodial branches [5, 6]. Here, we seek to understand how EC pseudopodial branching is locally regulated to directionally guide angiogenesis. We develop an in vitro 3D EC model system in which migrating ECs display branched pseudopodia morphodynamics similar to those in living zebrafish. Using this system, we find that ECM stiffness and ROCK-mediated myosin II activity inhibit EC pseudopodial branch initiation. Myosin II is dynamically localized to the EC cortex and is partially released under conditions that promote branching. Local depletion of cortical myosin II precedes branch initiation, and initiation can be induced by local inhibition of myosin II activity. Thus, local downregulation of myosin II cortical contraction allows pseudopodium initiation to mediate EC branching and hence guide directional migration and angiogenesis

Contamination des poissons par les corps radioactifs et décontamination. II. Etude sur la répartition physiologique du 45Ca insoluble chez Carassius auratus

Dumeste Marcel H., Gardel R., Delafolie P. Contamination des poissons par les corps radioactifs et décontamination. II. Etude sur la répartition physiologique du 45Ca insoluble chez Carassius auratus . In: Bulletin de l'Académie Vétérinaire de France tome 113 n°3, 1960. pp. 163-166

Hydrodynamic coupling and rotational mobilities near planar elastic membranes

We study theoretically and numerically the coupling and rotational hydrodynamic interactions between spherical particles near a planar elastic membrane that exhibits resistance towards shear and bending. Using a combination of the multipole expansion and Faxen's theorems, we express the frequency-dependent hydrodynamic mobility functions as a power series of the ratio of the particle radius to the distance from the membrane for the self mobilities, and as a power series of the ratio of the radius to the interparticle distance for the pair mobilities. In the quasi-steady limit of zero frequency, we find that the shear- and bending-related contributions to the particle mobilities may have additive or suppressive effects depending on the membrane properties in addition to the geometric configuration of the interacting particles relative to the confining membrane. To elucidate the effect and role of the change of sign observed in the particle self and pair mobilities, we consider an example involving a torque-free doublet of counterrotating particles near an elastic membrane. We find that the induced rotation rate of the doublet around its center of mass may differ in magnitude and direction depending on the membrane shear and bending properties. Near a membrane of only energetic resistance toward shear deformation, such as that of a certain type of elastic capsules, the doublet undergoes rotation of the same sense as observed near a no-slip wall. Near a membrane of only energetic resistance toward bending, such as that of a fluid vesicle, we find a reversed sense of rotation. Our analytical predictions are supplemented and compared with fully resolved boundary integral simulations where a very good agreement is obtained over the whole range of applied frequencies.Comment: 14 pages, 7 figures. Revised manuscript resubmitted to J. Chem. Phy

A Zyxin-Mediated Mechanism for Actin Stress Fiber Maintenance and Repair

SummaryTo maintain mechanical homeostasis, cells must recognize and respond to changes in cytoskeletal integrity. By imaging live cells expressing fluorescently tagged cytoskeletal proteins, we observed that actin stress fibers undergo local, acute, force-induced elongation and thinning events that compromise their stress transmission function, followed by stress fiber repair that restores this capability. The LIM protein zyxin rapidly accumulates at sites of strain-induced stress fiber damage and is essential for stress fiber repair and generation of traction force. Zyxin promotes recruitment of the actin regulatory proteins α-actinin and VASP to compromised stress fiber zones. α-Actinin plays a critical role in restoration of actin integrity at sites of local stress fiber damage, whereas both α-actinin and VASP independently contribute to limiting stress fiber elongation at strain sites, thus promoting stabilization of the stress fiber. Our findings demonstrate a mechanism for rapid repair and maintenance of the structural integrity of the actin cytoskeleton