Speaker: Dimitrios Vavylonis, Professor of Physics, Lehigh University

Title: Molecular Mechanisms and Self Organization of Subcellular Structures for Cell Division, Polarization and Motion

The ability of cells to divide, establish a polarization direction, and move by crawling requires the coordinated interactions of the cytoskeleton with membranes as well as with the signaling system organizing on membranes. A major challenge for mathematical and computational models of these mechanisms of subcellular organization is accounting of how highly specific interactions at the molecular level lead to the emergent collective cell behavior. We address aspects of this complexity by employing methods linking molecular to cellular scales, in collaboration with experimentalists working on model systems. Tubular fission yeast cells divide in the middle by forming an actomyosin contractile ring, anchored to the membrane by protein assemblies (“nodes”) containing globular as well as intrinsically disordered regions (IDRs). I will review prior Brownian dynamics modeling of actin ring-self-organization through node condensation. To understand how cells control node formation, we employed coarse-grained molecular dynamics showing how phosphorylation of the IDR of FBAR node-anchoring protein Cdc15 allows its oligomerization on the plasma membrane, as well as all-atom simulations of membrane binding of the other main node-anchoring protein, anllin-related Mid1. Growing (interphase) fission yeast cells direct actin polymerization towards their cell tip by membrane-bound Cdc42. To understand mechanisms in polarized cell growth, we used particle-based and continuum modeling of the Cdc42 system that establishes spatial patterns of activators and inhibitors on the cell membrane through a combination of nonlinear feedbacks and plasma membrane flows driven by polarized exocytosis. Time permitting, I will describe our work modeling the kinetics and mechanics of dendritic actin networks at the leading edge of polarized motile cells.

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