Geometry and Phase Behavior of Cell Membranes In Response to Curvature Inducing Proteins Investigated Using Field Theoretic as Well as Hybrid Particle-Field Simulation Methodologies
Neeraj Agrawal, Chemical and Biomolecular Engineering, University of Pennsylvania, 210 South 33rd Street, 240 Skirkanich Hall, Philadelphia, PA 19104, Jonathan Nukpezah, Bioengineering, University of Pennsylvania, 210 South 33rd Street, 240 Skirkanich Hall, Philadelphia, PA 19104, and Ravi Radhakrishnan, Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, 240 Skirkanich Hall, Philadelphia, PA 19104.
Internalization of extracellular cargo by eukaryotic cells into their cytoplasm via the endocytic machinery is an important regulatory process required for a large number of essential cellular functions. Endocytosis is orchestrated by a variety of proteins. These proteins are implicated in membrane deformation/bending, cargo recognition and vesicle scision. Since, the process of endocytosis happens on sub-micrometer length scale, a coarse-grained membrane Hamiltonian is more appropriate to describe the relevant processes. We present two methodologies to describe the membrane deformation due to curvature inducing proteins such as Epsin. First methodology integrates protein diffusion on the cell membrane and the cell membrane deformation using a combination of Monte-Carlo and the Time dependent Ginzburg Landau formalism with a Helfrich Hamiltonian. A rich variety of membrane phase behavior is obtained by varying the extent and degree of induced curvature and the concentration of proteins on the membrane. However, the first approach cannot adequately describe membrane shapes characterized by overhangs. Large membrane deformation is seen in the later stages of membrane vesicle formation. Using surface evolution approach, we describe membrane geometries in large deformation limit under the assumptions of axis-symmetry. We evaluate different modes of induction of vesicles on a cell membrane in the presence of molecular assemblies of curvature inducing proteins.