(751d) Self-Assembled Protein Structures Are Altered By Underlying Fluctuations
AIChE Annual Meeting
2013
2013 AIChE Annual Meeting
Materials Engineering and Sciences Division
Nanoscale Phenomena in Macromolecular Systems
Thursday, November 7, 2013 - 4:25pm to 4:45pm
Clathrin proteins stabilize the budding and curvature of cell membranes that are characteristic of endocytosis, an essential process by which cells internalize nutrients and other cargo. Clathrin’s robust ability to self-assemble in vitro into a variety of structures depending on experimental conditions also makes it a promising tool for templating inorganic nanostructures. Observations of clathrin aggregation on membranes in vivo show the formation of two distinct structures, dependent on membrane conditions [Saffarian et al., PLoS Biology, 2009, 7, e1000191]. Specifically, large, flat “plaques” are observed predominantly where the underlying membrane is adhered to a rigid substrate, while short-lived, curved “pits” are found on all membrane surfaces. These findings indicate that cellular transport may be modulated by subtle physical changes in the mechanical properties of cell membranes, and have important implications for systems self-assembling on flexible substrates in general. We develop a simplified physical model of clathrin proteins coupled to a membrane. This model is used in Monte Carlo simulations and analytical theory to show the effect of membrane fluctuations on the phase behavior of clathrin lattices. Crystalline, plaque-like lattices are stabilized when membrane tension is much higher than its physiological value, thereby suppressing thermal membrane fluctuations. Inversely, large membrane fluctuations give rise to disordered, fluid clathrin phases. Our observations are quantified through correlation functions of lattice order. We also predict the response of clathrin assemblies to indentations of the membrane similar to those felt during endocytosis. Fluid lattices, brought about by membrane fluctuations at low tension, are shown to be more capable of coating these indentations than crystalline lattices, which typically result in tearing of the lattice and generation of void spaces localized to the indentation. These findings illustrate how the mechanical properties of membranes dictate the nature of their associated protein aggregates, thereby explaining experimental observations regarding disparate clathrin phases on different cell surfaces. This useful insight on the role that physical properties of the surrounding environment have in self-assembly on surfaces can result in better understanding of biological processes and guidance of bio-templated nanotechnology.