Biophysical Society Thematic Meeting| Padova 2019

Quantitative Aspects of Membrane Fusion and Fission

Tuesday Speaker Abstracts

BIOPHYSICS OF MEMBRANE CURVATURE REMODELING AT MOLECULAR AND MESOSCOPIC LENGTH SCALES Ravi Radhakrishnan 1 ; 1 University of Pennsylvania, Bioengineering, Philadelphia, Pennsylvania, USA At the micron scale, cell organelles display an amazing complexity in their shape and organization. The physical properties of a biological membrane can be understood using continuum models subject to thermal undulations. Yet, the chief orchestrators of these complex and intriguing shapes are a specialized class of membrane associating often peripheral proteins called curvature remodeling proteins (CRPs) that operate at the molecular level through protein- lipid interactions. We discuss multiscale methodologies to model these systems at the molecular and the cellular scales, and present an energy landscape perspective of membrane remodeling through the organization and assembly of CRPs. We discuss the morphological space of nearly planar to highly curved membranes, methods to include thermal fluctuations, and review studies that model such proteins as curvature fields to describe the emergent curved morphologies. We also discuss several mesoscale models applied to a variety of cellular processes, where the phenomenological parameters are determined using molecular simulations. Much insight can be gained from the calculation of free energies of membranes states with protein fields, which enable accurate mapping of the state and parameter values at which the membrane undergoes morphological transformations such as vesiculation or tubulation. By tuning the strength, anisotropy, and spatial organization of the curvature-field, one can generate a rich array of membrane morphologies that are highly relevant to shapes of several cellular organelles. We review describe of these models to budding of vesicles commonly seen in cellular signaling and trafficking processes such as clathrin mediated endocytosis, sorting by the ESCRT protein complexes, and cellular exocytosis regulated by the exocyst complex. We discuss future prospects where such models can be combined with other models for cytoskeletal assembly, and discuss their role in understanding the effects of cell membrane tension and the mechanics of the extracellular microenvironment on cellular processes.

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