(112g) Multiscale Simulations of Curvature Inducing Protein Partitioning in the Presence of Mean and Gaussian Curvature Gradients

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.

References:

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2. 
Systems Biology and Physical Biology of Clathrin-Mediated
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3.       Mesoscale Modeling and Simulations of Spatial Partitioning
of Curvature Inducing Proteins under the Influence of Mean Curvature Fields in
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Radhakrishnan, Molecular Physics, 2012, in press. (DOI:10.1080/00268976.2012.664661)