The separation of an inside from an outside lies at the very heart of cellular life, and the organization of living organisms into cells and sub-cellular compartments is required for a large number of biological functions. This compartmentalization is maintained by lipid bilayers and undergoes frequent but carefully regulated topological changes, such as pore formation, fusion, and fission. Changes of membrane topology are involved in a variety of basic, cellular processes and require lipid rearrangements and transient formation of non-bilayer intermediate structures driven by curvature stress. We study the mechanisms of these processes by coarse-grained models, obtaining the minimum free-energy path via self-consistent field theory.
Division of intracellular organelles culminates with the scission of a highly constricted membrane neck. During fission, the tube first partially collapses into a worm-like micelle or hemifission (HF) intermediate, which then ruptures, resulting in two capped tubes. When unaided, the free-energy barriers for such remodeling can be prohibitively high, so biological systems employ proteins as catalysts. Simply constricting the membrane aids the initial partial collapse, however, dynamin — a common fission protein — also inserts itself between head groups, distorting the membrane. Our results suggest that this distortion plays a critical role in reducing the free energy barrier to fission.
Fission often correlates with additional membrane wrapping, e.g. by the endoplasmic reticulum (ER) or the extra membrane of the mitochondrion. Such a wrapping plays a vital role in proteome and lipidome organization, yet its impact on the free-energy landscape of the fission process has largely remained unexplored. We investigate the stress-induced instabilities brought about by membrane wrapping in a simple double-membrane tubular system. We find that an outer membrane facilitates an alternative pathway for the fission of the inner tube at physiologically relevant membrane tensions. This alternative pathway results from a transient contact between the membranes of the inner and outer tube. A detailed study of the fission pathways in a double-membrane tubular system reveals the topological complexity of the process, resulting both in leaky and leakless intermediates.

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