Charles University, Faculty of Mathematics and Physics, Mathematical Institute, Sokolovská 83, 186 75 Prague 8, Czech Republic.
Institute of Chemistry, The Fritz Haber Center, and The Center for Nanoscience and Nanotechnology, The Hebrew University, E.J. Safra Campus, Jerusalem 9190401, Israel.
ACS Nano. 2021 Aug 24;15(8):12880-12887. doi: 10.1021/acsnano.0c08614. Epub 2021 Aug 2.
Vesicles enriched in certain negatively charged lipids, such as phosphatidylserine and PIP2, are known to undergo fusion in the presence of calcium ions without assistance from protein assemblies. Other lipids do not exhibit this propensity, even if they are negatively charged. Using our recently developed methodology, we extract elastic properties of a representative set of lipids. This allows us to trace the origin of lipid-calcium selectivity in membrane fusion to the formation of lipid clusters with long-range correlations that induce negative curvature on the membrane surface. Furthermore, the clusters generate lateral tension in the headgroup region at the membrane surface, concomitantly also stabilizing negative Gaussian curvature. Finally, calcium binding also reduces the orientational polarization of water around the membrane head groups, potentially reducing the hydration force acting between membranes. Binding calcium only weakly increases membrane bending rigidity and tilt moduli, in agreement with experiments. We show how the combined effects of calcium binding to membranes lower the barriers along the fusion pathway that lead to the formation of the fusion stalk as well as the fusion pore.
已知富含某些带负电荷的脂质（如磷脂酰丝氨酸和 PIP2）的囊泡在钙离子存在下无需蛋白质组装的帮助即可融合。其他脂质即使带负电荷也不会表现出这种倾向。使用我们最近开发的方法，我们提取了一组代表性脂质的弹性特性。这使我们能够将脂质-钙选择性追溯到在膜融合中诱导膜表面负曲率的长程相关脂质簇的形成。此外，这些簇在膜表面的头部区域产生横向张力，同时也稳定负高斯曲率。最后，钙结合还降低了围绕膜头部基团的水分子的取向极化，可能会降低膜之间的水合力。钙结合仅微弱地增加膜弯曲刚性和倾斜模量，这与实验结果一致。我们展示了钙与膜结合如何降低融合途径中形成融合柄和融合孔的屏障。
