Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

23-POS Board 23 LIPIDOMICS VIEW ON FREE ENERGIES OF PORE AND STALK FORMATION IN AND BETWEEN MEMBRANES Chetan S Poojari 1 ; Katharina Scherer 1 ; Gari Kasparyan 1 ; Jochen S Hub 1 ; 1 Saarland University, Theoretical Physics, Saarbrücken, Germany Many biological membranes are asymmetric and exhibit complex lipid composition, comprising hundreds of distinct chemical species. Identifying the biological function and advantage of this complexity is a central goal of membrane biology. We use MD simulations at atomic and coarse- grained resolution to reveal how complex lipid compositions control the free energy landscape of topological transitions of membranes, including the formation of fusion stalks or trans-membrane pores. We find that the inner leaflet of a typical plasma membrane is far more fusogenic than the outer leaflet, which is likely an adaptation to evolutionary pressure. To rationalize these findings by the distinct lipid compositions of the membrane leaflets, we computed ~200 free energies of stalk formation between membranes of different lipid content, providing a comprehensive fusogenicity map of many biologically relevant lipid classes. In addition, we investigate how lipid-protein interactions and transmembrane potentials shape the landscape of membrane transitions. We find that membrane-binding proteins motifs from viral fusion proteins may control membrane fusion; their impact, however, greatly depends on geometry of the membrane- interacting peptide and on lipid composition. Together, our simulations provide a quantitative view on the role of lipid content and lipid-protein interactions during topological transitions of membranes.

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