Free energies of membrane stalk formation from a lipidomics perspective

• Published in: Nature communications 2021-11, Vol.12 (1), p.6594-6594, Article 6594
• Main Authors: Poojari, Chetan S., Scherer, Katharina C., Hub, Jochen S.
• Format: Article
• Language: English
• Subjects: 631/45/287/1192; 631/57/2266; 631/57/2270; 631/80/313/2378; Biological membranes; Biophysics; Cell Membrane - chemistry; Cell membranes; Chemical speciation; Complexity; Composition; Computational Biology; Computational efficiency; Entropy; Humanities and Social Sciences; Kinetics; Lipid composition; Lipidomics - methods; Lipids; Membrane Fusion; Membranes; Membranes - chemistry; multidisciplinary; Phospholipids; Science; Science (multidisciplinary); Simulation; Thermodynamics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26924-2

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. Here, we study how membrane complexity controls the energetics of the first steps of membrane fusions, that is, the formation of a stalk. We first present a computationally efficient method for simulating thermodynamically reversible pathways of stalk formation at coarse-grained resolution. The method reveals 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, we computed ~200 free energies of stalk formation in membranes with different lipid head groups, tail lengths, tail unsaturations, and sterol content. In summary, the simulations reveal a drastic influence of the lipid composition on stalk formation and a comprehensive fusogenicity map of many biologically relevant lipid classes. Fusion of cellular membranes begins with the formation of a stalk. Here, the authors develop a computationally efficient method for coarse-grained simulations of stalk formation and apply this approach to comprehensively analyse how stalk formation is influenced by the membrane lipid composition.