(268b) Thermodynamics of Protein-Mediated Self Assembly On Cell Membranes

     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.