Kandy Sreeja K, Janmey Paul A, Radhakrishnan Ravi
Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA.
Department of Physiology, University of Pennsylvania, Philadelphia, PA.
Curr Opin Syst Biol. 2021 Mar;25:34-41. doi: 10.1016/j.coisb.2021.02.001. Epub 2021 Feb 25.
We opine on the recent advances in experiments and modeling of modular signaling complexes assembled on mammalian cell membranes (membrane signalosomes) in the context of several applications including intracellular trafficking, cell migration, and immune response. Characterizing the individual components of the membrane assemblies at the nanoscale, ranging from protein-lipid and protein-protein interactions, to membrane morphology, and the energetics of emergent assemblies at the subcellular to cellular scales pose significant challenges. Overcoming these challenges through the iterative coupling of multiscale modeling and experiment can be transformative in terms of addressing the gaps between structural biology and super-resolution microscopy, as it holds the key to the discovery of fundamental mechanisms behind the emergence of function in the membrane signalosome.
我们针对在包括细胞内运输、细胞迁移和免疫反应等多种应用背景下，在哺乳动物细胞膜上组装的模块化信号复合体（膜信号体）的实验和建模方面的最新进展发表意见。在纳米尺度上表征膜组装体的各个组成部分，从蛋白质-脂质和蛋白质-蛋白质相互作用到膜形态，以及在亚细胞到细胞尺度上新兴组装体的能量学，都构成了重大挑战。通过多尺度建模与实验的迭代耦合来克服这些挑战，在弥合结构生物学与超分辨率显微镜之间的差距方面可能具有变革性，因为它是发现膜信号体功能出现背后基本机制的关键。
