A master relation defines the nonlinear viscoelasticity of single fibroblasts

Cell mechanical functions like locomotion, contraction and division are controlled by the cytoskeleton, a dynamic biopolymer network whose mechanical properties remain poorly understood. We perform single-cell uniaxial stretching experiments on 3T3 fibroblasts. By superimposing small amplitude oscillations on a mechanically prestressed cell, we find a transition from linear viscoelastic behavior to power-law stress stiffening. Data from different cells over several stress decades can be uniquely scaled to obtain a master-relation between the viscoelastic moduli and the average force. Remarkably, this relation holds independently of deformation history, adhesion biochemistry, and intensity of active contraction. In particular, it is irrelevant whether force is actively generated by the cell or externally imposed by stretching. We propose that the master-relation reflects the mechanical behavior of the force bearing actin cytoskeleton, in agreement with stress stiffening known from semiflexible filament networks.Comment: 12 pages, 11 figures. Accepted for publication in Biophysical Journal, scheduled to appear in May 200

Dynamics of Membrane Tethers Reveal Novel Aspects of Cytoskeleton-Membrane Interactions in Axons

AbstractMechanical properties of cell membranes are known to be significantly influenced by the underlying cortical cytoskeleton. The technique of pulling membrane tethers from cells is one of the most effective ways of studying the membrane mechanics and the membrane-cortex interaction. In this article, we show that axon membranes make an interesting system to explore as they exhibit both free membrane-like behavior where the tether-membrane junction is movable on the surface of the axons (unlike many other cell membranes) as well as cell-like behavior where there are transient and spontaneous eruptions in the tether force that vanish when F-actin is depolymerized. We analyze the passive and spontaneous responses of axonal membrane tethers and propose theoretical models to explain the observed behavior

The role of the cytoskeleton in volume regulation and beading transitions in PC12 neurites

We present investigations on volume regulation and beading shape transitions in PC12 neurites conducted using a flow-chamber technique. By disrupting the cell cytoskeleton with specific drugs we investigate the role of its individual components in the volume regulation response. We find that microtubule disruption increases both swelling rate and maximum volume attained, but does not affect the ability of the neurite to recover its initial volume. In addition, investigation of axonal beading --also known as pearling instability-- provides additional clues on the mechanical state of the neurite. We conclude that the initial swelling phase is mechanically slowed down by microtubules, while the volume recovery is driven by passive diffusion of osmolites. Our experiments provide a framework to investigate the role of cytoskeletal mechanics in volume homeostasis

Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells.

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells

Coarsening through directed droplet coalescence in fluid-fluid phase separation

Phase-separation dynamics of an asymmetric mixture of an isotropic dopant in a nematogenic fluid is presented. We show that, on steady cooling, the nucleating nematic drops move down the dopant concentration gradient, with a velocity that is dependent on the cooling rate and concentration gradient. This propulsion of the drops leads to a mechanism of droplet coarsening, where radius of a drop scales with time as R(t)∼t. Various mechanisms for droplet propulsion are discussed

Self-propulsion of nematic drops: novel phase separation dynamics in impurity-doped nematogens

We report a novel phase separation dynamics, mediated by self-propelled motion of the nucleated drops, in a mixture of a nematogen and an isotropic dopant. We show that surface flow, induced by the gradient in the concentration of the dopant expelled by the growing drops, provides the driving force for the propulsion of nematic droplets. While the liquid crystal-isotropic transition is used here to demonstrate the phenomenon, self-propulsion should be observable in many other systems in which the dynamics of a conserved order parameter is coupled to a nonconserved order parameter