275675 Multiscale Simulations of Curvature Inducing Protein Partitioning in the Presence of Mean and Gaussian Curvature Gradients

Monday, October 29, 2012: 2:30 PM
415 (Convention Center )
Richard Tourdot, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, Ryan P. Bradley, Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, Natesan Ramakrishnan, UPenn, Philadelphia, PA and Ravi Radhakrishnan, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA

Cell membrane remodeling processes such as endocytosis and cell motility require dynamic curvature induction of the lipid bilayer. These cellular processes are driven by proteins domains such as the Epsin ENTH domain and the Ampiphysin NBAR domain, which coordinate with the mem- brane phospholipid PIP2 and impart asymmetric lateral stresses on the bilayer. These curvature inducing proteins are also thought to sense curvature gradients along the membrane. In clathrin mediated endocytosis, the assembly of the clathrin coat and the invagination of the vesicle occur simultaneously. During this process Epsins relocate to the budding vesicle and combine with the growing clathrin coat. As a spherical bud begins to form ampiphysins are thought to relocate to the neck of the budding vesicle and recruit dynamin. Endocytosis concludes when dynamin pinches the bud and releases a vesicle into the cytoplasm. It has been shown experimentally that epsins cluster onto regions of background membrane curvature. These clustering effects are thought to be present during endocytosis. Evidence of segregation of curvature inducing proteins during membrane remodeling processes has motivated this study of their clustering properties in curvature gradients. Our membrane Monte Carlo (MMC) model incorporates a dynamically triangulated mesh with curvilinear coordinates. This model is evolved using the Helfrich Hamiltonian. In a previous study, we investigated the role of clathrin using a one-dimensional membrane model. This model determined a critical clathrin coat size above which a mature bud with a well defined neck region could form. The curvilinear membrane model used in this study replicated this previous finding, with clathrin coat sizes greater than 2000nm2 yielding mature buds. Here, we show  that Epsin segregation initially increases as the clathrin coat grows. We also show that Epsin segregation plateaus after reaching a critical coat radius where the membrane can adopt fully formed bud geometries. The distribution of epsins within the bud is quantified.


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