Larsen Jannik B, Rosholm Kadla R, Kennard Celeste, Pedersen Søren L, Munch Henrik K, Tkach Vadym, Sakon John J, Bjørnholm Thomas, Weninger Keith R, Bendix Poul Martin, Jensen Knud J, Hatzakis Nikos S, Uline Mark J, Stamou Dimitrios
Bionanotecnology and Nanomedicine Laboratory, University of Copenhagen, Copenhagen, Denmark.
Nano-Science Center, University of Copenhagen, Copenhagen, Denmark.
ACS Cent Sci. 2020 Jul 22;6(7):1159-1168. doi: 10.1021/acscentsci.0c00419. Epub 2020 Jun 23.
Biological membranes have distinct geometries that confer specific functions. However, the molecular mechanisms underlying the phenomenological geometry/function correlations remain elusive. We studied the effect of membrane geometry on the localization of membrane-bound proteins. Quantitative comparative experiments between the two most abundant cellular membrane geometries, spherical and cylindrical, revealed that geometry regulates the spatial segregation of proteins. The measured geometry-driven segregation reached 50-fold for membranes of the same mean curvature, demonstrating a crucial and hitherto unaccounted contribution by Gaussian curvature. Molecular-field theory calculations elucidated the underlying physical and molecular mechanisms. Our results reveal that distinct membrane geometries have specific physicochemical properties and thus establish a ubiquitous mechanistic foundation for unravelling the conserved correlations between biological function and membrane polymorphism.
生物膜具有独特的几何形状，赋予其特定的功能。然而，现象学上几何形状/功能相关性背后的分子机制仍然难以捉摸。我们研究了膜几何形状对膜结合蛋白定位的影响。在两种最丰富的细胞膜几何形状——球形和圆柱形之间进行的定量比较实验表明，几何形状调节蛋白质的空间分离。对于具有相同平均曲率的膜，测得的由几何形状驱动的分离可达50倍，这表明高斯曲率起到了关键且迄今未被考虑的作用。分子场理论计算阐明了潜在的物理和分子机制。我们的结果表明，不同的膜几何形状具有特定的物理化学性质，从而为揭示生物功能与膜多态性之间的保守相关性建立了一个普遍的机制基础。
