2009 Math Biology Seminar - 03

Formation of endocytic vesicles is a complex, dynamic process that couples sequential protein recruitment and lipid modifications with dramatic shape transformations of the plasma membrane. How the proper timing and coordination of these events is achieved, and the vesicle scission mechanism, are not understood. We address these questions by constructing an integrated mathematical model based on four key ideas: (1) membrane curvature and PI(4,5)P2 hydrolysis are mechanochemically coupled; (2) curvature-sensing and curvature-deforming activities constitute a positive feedback loop for BAR domain protein recruitment; (3) the mechanochemical coupling of events ensures the proper and robust temporal and spatial sequence of endocytic events; and (4) vesicle scission is the result of an interfacial force that develops at a lipid phase boundary. The model quantitatively recapitulates the endocytic events in budding yeast in a coherent manner, and explains key aspects of endocytosis in mammalian cells.