A pinboard by
Fowad Motahari

Physics Ph.D. Candidate, Washington University in St. Louis


Pulling forces in endocytosis are being generated by actin polymerization.

In the process of endocytosis, by which the cell plasma membrane invaginate inward in order to bring the essential extracellular proteins into the cytoplasm, there are many different proteins that play their roles. Among them actin monomers are the main players; As previous super-resolution microscope experiments have shown, the membrane curving does not initiate until the actin monomers arrive at the endocytic patch. Actin monomers form filamentous long structures in an area of about 200 nm squared wide beneath the membrane, where the same filaments exerts pushing and pulling forces on the membrane. The mechanism behind the generation of the pushing force by the growth of an actin filament (actin polymerization) is pretty well-understood and modeled; The famous Brownian Ratchet model is an example of a simple picture on how such polymerization generates force to push on an obstacle ahead. However, we know that in endocytosis, the membrane's curvature is progressing inward to form a drop shape pit that will get pinched off eventually into a vesicle, carrying proteins into the cell cytoplasm. Therefore, at the center of this endocytic patch, pulling forces are being exerted on the membrane to derive the invagination. Studying the mechanism behind the generation of these pulling forces, caused by the growth of the actin filaments, is the main focus of my research. Our hypothesis is that the retrograde movement of the entire actin network in the endocytic patch is the force behind the curvature generation in the form that we see on the cell membrane. Recent experimental findings confirm the existence of a specific protein called Sla2, that acts as a glue connecting protein that holds the slower growing filaments at the center of the endocytic patch and keeps them connected to the membrane (like a hook, that in physical terms is a potential well) Consequently, the retrograde motion of the whole actin network based on the actin polymerization, can naturally lead to the membrane curvature and endocytosis.


Load sharing in the growth of bundled biopolymers.

Abstract: To elucidate the nature of load sharing in the growth of multiple biopolymers, we perform stochastic simulations of the growth of biopolymer bundles against obstacles under a broad range of conditions and varying assumptions. The obstacle motion due to thermal fluctuations is treated explicitly. We assume the "Perfect Brownian Ratchet" (PBR) model, in which the polymerization rate equals the free-filament rate as soon as the filament-obstacle distance exceeds the monomer size. Accurate closed-form formulas are obtained for the case of a rapidly moving obstacle. We find the following: (1) load sharing is usually sub-perfect in the sense that polymerization is slower than for a single filament carrying the same average force; (2) the sub-perfect behavior becomes significant at a total force proportional to the logarithm or the square root of the number of filaments, depending on the alignment of the filaments; (3) for the special case of slow barrier diffusion and low opposing force, an enhanced obstacle velocity for an increasing number of filaments is possible; (4) the obstacle velocity is very sensitive to the alignment of the filaments in the bundle, with a staggered alignment being an order of magnitude faster than an unstaggered one at forces of only 0.5 pN per filament for 20 filaments; (5) for large numbers of filaments, the power is maximized at a force well below 1 pN per filament; (6) for intermediate values of the obstacle diffusion coefficient, the shape of the force velocity relation is very similar to that for rapid obstacle diffusion.

Pub.: 10 Dec '14, Pinned: 29 Jun '17