Binding constants of membrane-anchored receptors and ligands depend strongly on the nanoscale roughness of membranes
Binding constants of membrane-anchored receptors and ligands depend strongly on the nanoscale roughness of membranes
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DOI：
10.1073/pnas.1305766110
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发表时间：
2013-09-17
影响因子：
11.1
通讯作者：
Weikl, Thomas R.
中科院分区：
文献类型：
--
作者：
Hu, Jinglei;Lipowsky, Reinhard;Weikl, Thomas R.
细胞黏附和囊泡与细胞膜或细胞器的黏附是免疫反应、组织形成和细胞信号传递的关键。黏附过程敏感地依赖于介导黏附的膜锚定受体和配体蛋白的结合常数，但在实验中很难测量这个常数。我们用分子动力学模拟研究了膜锚定受体和配体蛋白的结合。我们发现，在纳米尺度上，由于热激发膜形状的波动，锚定蛋白的结合常数随着膜粗糙度的增大而显著减小。我们提出了一种理论，解释了膜约束锚定蛋白质结合常数的粗糙度依赖关系，并将该常数与没有膜锚定的可溶性蛋白质的结合常数联系起来。由于可溶性蛋白质的结合常数在实验中很容易获得，我们的结果为计算膜锚定受体和配基蛋白质的结合常数提供了一个有用的途径。
Cell adhesion and the adhesion of vesicles to the membranes of cells or organelles are pivotal for immune responses, tissue formation, and cell signaling. The adhesion processes depend sensitively on the binding constant of the membrane-anchored receptor and ligand proteins that mediate adhesion, but this constant is difficult to measure in experiments. We have investigated the binding of membrane-anchored receptor and ligand proteins with molecular dynamics simulations. We find that the binding constant of the anchored proteins strongly decreases with the membrane roughness caused by thermally excited membrane shape fluctuations on nanoscales. We present a theory that explains the roughness dependence of the binding constant for the anchored proteins from membrane confinement and that relates this constant to the binding constant of soluble proteins without membrane anchors. Because the binding constant of soluble proteins is readily accessible in experiments, our results provide a useful route to compute the binding constant of membrane-anchored receptor and ligand proteins.