A Coarse-grained Model for the Formation of Caveolae

1. n rtransverse rnormal r A Coarse-grained Model for the Formation of Caveolae Investigators: L E Wedgewood, L C Nitsche, B Akpa: Chemical Engineering; R D Minshall, Pharmacology and Anesthesiology Primary Grant Support: National Institutes of Health • Animal cell membrane regions rich in the protein caveolin form ~50 nm pits or indentations (‘caveolae’) [Fig. 1] • Caveolae accept molecular cargo that is to be absorbed by the cell, thus forming endocytic vesicles [Fig. 2] • roles in signaling, cholesterol trafficking, pathogen invasion • disruption of caveolin expression is linked to disease • Current microscopic techniques cannot be used to continuously observe the process of formation of specific caveolae • Coarse-grained approaches can be used to feasibly study interactions of caveolins with the lipid bilayer that result in the formation of caveolae [Figs. 3 and 4] Fig. 1Caveolae are ~50 nm indentations at cell surfaces Fig 2Caveolae accept molecules to be absorbed into the cell (endocytosis) Fig. 4 A section-view of the membrane model Fig. 3 Increasingly coarse-grained models of lipid bilayer phospholipids • The lipid bilayer is modeled as a coarse-grained 2D fluid [Fig. 3] • each particle in the model represents a cluster of phospholipids • 2D structure is preserved using a combination of potentials that [Fig. 4] • favor a specified minimum inter-particle distance • cause particles to be attracted to one another • penalize particles for leaving the 2D surface • Computation is saved by only considering interactions with neighboring particles • particle interactions restricted to specified cutoff distances • Caveolins modeled as bead-spring chains • subject to Brownian forces • Lipid membrane modeled as a stable 2D fluid • Various kinds of surfaces modeled • plane, sphere, hemisphere • Physical properties of model are being investigated • to confirm that model exhibits typical lipid-bilayer characteristics • Future goals • to incorporate caveolin proteins on the bilayer • to model the cytoskeleton and its interactions • to model the pinch-off of invaginated surface caveolae to form endocytic vesicles