279164 Thermodynamics of Protein-Mediated Self Assembly On Cell Membranes

Tuesday, October 30, 2012: 12:51 PM
411 (Convention Center )
Natesan Ramakrishnan and Ravi Radhakrishnan, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA

     In eukaryotic cells, the internalization of extracellular cargo into the cytoplasm via the endocytosis machinery is an important regulatory process required for a large number of essential cellular functions, including nutrient uptake, cell-cell communication, and modulation of cell-membrane composition. Endocytosis is orchestrated by a variety of proteins. These proteins are implicated in membrane deformation/bending, cargo recognition and vesicle scission.    While the involvement of these proteins have been established and their roles in membrane deformation, cargo recognition, and vesicle scission have been identified, current conceptual understanding falls short of a mechanistic description of the cooperativity and the bioenergetics of the underlying vesicle formation and growth which we address here using theoretical models based on an elastic continuum representation for the membrane and coarse-grained representations for the proteins. We present a quantitative model for describing how cell-membrane topologies are actively mediated and manipulated by intracellular protein assemblies. We formulate a minimal model by restricting our focus to a few proteins in the clathrin coat assembly: clathrin, epsin and AP-2, and BAR-domains and their role in the stabilization of various budding morphologies on the cell membrane. We describe the energetics of (topologically-invariant) deformation in planar membranes as well as in membranes with intrinsic curvature by the Helfrich Hamiltonian coupled with orderparameters associated with protein arrangements. Our approach is versatile in describing membrane geometries in both small and large deformation limits and for arbitray shapes and thermal undulations of the membrane. Our results yield membrane energies as well as entropy changes. A rich variety of membrane phase behavior is obtained by varying the extent and degree of induced curvature and the concentration of epsins and BAR domains on the membrane.

References

1.  Minimal Mesoscale Model for Protein-Mediated Vesiculation in Clathrin-Dependent Endocytosis, N.J. Agrawal, J. Nukpezah, R. Radhakrishnan, PLoS: Computational Biology, 6(9) e1000926, 2010. doi:10.1371/journal.pcbi.1000926. Pubmed ID: 20838575.

2.  Systems Biology and Physical Biology of Clathrin-Mediated Endocytosis: An Integrative Experimental and Theoretical Perspective, V. Ramanan, N. J. Agrawal, J. Liu, S. Engles, R. Toy, R. Radhakrishnan, Integrative Biology (RSC Journal), 2011, 3(8), 803-815. DOI: 10.1039/c1ib00036e. Pubmed ID: 21792431.

3.  Mesoscale Modeling and Simulations of Spatial Partitioning of Curvature Inducing Proteins under the Influence of Mean Curvature Fields in Bilayer Membranes, J. Liu, R. Tourdot, V. Ramanan, N. J. Agrawal, R. Radhakrishnan, Molecular Physics, 2012, in press. (DOI:10.1080/00268976.2012.664661)

4. N. Ramakrishnan, R. Radhakrishnan, to be published.


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See more of this Session: Computational Studies of Self-Assembly II
See more of this Group/Topical: Engineering Sciences and Fundamentals