Enhanced Nucleocytoplasmic Transport due to Competition for Elastic Binding Sites.

Nuclear pore complexes (NPCs) control all traffic into and out of the cell nucleus. NPCs are molecular machines that simultaneously achieve high selectivity and high transport rates. The biophysical details of how cargoes rapidly traverse the pore remain unclear but are known to be mediated by interactions between cargo-binding chaperone proteins and natively unstructured nucleoporin proteins containing many phenylalanine-glycine repeats (FG nups) that line the pore's central channel. Here, we propose a specific and detailed physical mechanism for the high speed of nuclear import based on the elasticity of FG nups and on competition between individual chaperone proteins for FG nup binding. We develop a mathematical model to support our proposed mechanism. We suggest that the recycling of nuclear import factors back to the cytoplasm is important for driving high-speed import and predict the existence of an optimal cytoplasmic concentration of cargo for enhancing the rate of import over a purely diffusive rate.

Cytoskeletal chirality: swirling cells tell left from right.

A new study reports that dynamic actin fibers in cells on circular islands self-organize into a swirling counter-clockwise pattern and describes a basic cytoskeletal mechanism for the establishment of left-right asymmetry that is based on myosin contraction and twisting of the formin-actin filament.

A mechanism of leading-edge protrusion in the absence of Arp2/3 complex.

Cells employ protrusive leading edges to navigate and promote their migration in diverse physiological environments. Classical models of leading-edge protrusion rely on a treadmilling dendritic actin network that undergoes continuous assembly nucleated by the Arp2/3 complex, forming ruffling lamellipodia. Recent work demonstrated, however, that, in the absence of the Arp2/3 complex, fibroblast cells adopt a leading edge with filopodia-like protrusions (FLPs) and maintain an ability to move, albeit with altered responses to different environmental signals. We show that formin-family actin nucleators are required for the extension of FLPs but are insufficient to produce a continuous leading edge in fibroblasts lacking Arp2/3 complex. Myosin II is concentrated in arc-like regions of the leading edge in between FLPs, and its activity is required for coordinated advancement of these regions with formin-generated FLPs. We propose that actomyosin contraction acting against membrane tension advances the web of arcs between FLPs. Predictions of this model are verified experimentally. The dependence of myosin II in leading-edge advancement helps explain the previously reported defect in directional movement in the Arpc3-null fibroblasts. We provide further evidence that this defect is cell autonomous during chemotaxis.

Computational estimates of membrane flow and tension gradient in motile cells.

All parts of motile cells, including the plasma membrane, have to translocate in the direction of locomotion. Both directed intracellular membrane transport coupled with polarized endo- and exocytosis and fluid flow in the plane of the plasma membrane can contribute to this overall plasma membrane translocation. It remains unclear how strong a force is required to generate this flow. We numerically solve Stokes equations for the viscous membrane flow across a flat plasma membrane surface in the presence of transmembrane proteins attached to the cytoskeleton and find the membrane tension gradient associated with this flow. This gradient is sensitive to the size and density of the transmembrane proteins attached to the cytoskeleton and can become significant enough to slow down cell movement. We estimate the influence of intracellular membrane transport and actin growth and contraction on the tension gradient, and discuss possible 'tank tread' flow at ventral and dorsal surfaces.