Modeling cell crawling MEP or BEP - BN / Idema group - theoretical biophysics Epithelial cells (the type of cells lining surfaces in your body, such as the inside of your eyes, your blood vessels, and your skin - the most abundant cell type) can crawl across a surface using lamellipodia. A lamellipodium is a sheet-like extension of the cell across the surface, filled with actin fibers, shown in red in the image on the right. Lamellipodia grow by actin polymerization, and are part of a continuous dynamical process of cytoskeletal construction and disassembly. This process is responsible for creating forces in the cell, which in turn are used to pull the cell forward. To do so, they need to make physical connection with the surface underneath, which they do through focal contacts. In this project, youʼll model lamellipodium dynamics and cell motility using a course-grained description in which the lamellipodium is chopped up in parts roughly equal in size to the region of a focal contact so much smaller than the lamellipodium itself, but much larger than an actin filament. Using a basic set of rules for the interaction of these parts, youʼll study their dynamics, as they stochastically explore the space around the cell. To do so, youʼll perform molecular dynamics simulations, in which you calculate the forces on each part, and use those to calculate their instantaneous velocities and displacements. Youʼll also calculate stresses generated by the lamellipodium, and use those to match your simulations to experimental observations. Migrating epithelial mouse cell with a lamellipodium extension. The leading edge is the red curve, rich in actin, one of the cytoskeletal fibers in the cell. On the trailing edge, a protein called cofilin (shown in green) disassembles the actin. The blob-like object near the read is the cell nucleus. image source: http:// www.bpod.mrc.ac.uk/archive/2012/1/17
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