Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
J Membr Biol. 2022 Jun;255(2-3):175-184. doi: 10.1007/s00232-022-00228-y. Epub 2022 Mar 25.
Curvature-inducing proteins are involved in a variety of membrane remodeling processes in the cell. Several in vitro experiments have quantified the curvature sensing behavior of these proteins in model lipid systems. One such system consists of a membrane bilayer laid atop a wavy substrate (Hsieh in Langmuir 28:12838-12843, 2012). In these experiments, the bilayer conforms to the wavy substrate, and curvature-inducing proteins show preferential segregation on the wavy membrane. Using a mesoscale computational membrane model based on the Helfrich Hamiltonian, here we present a study which analyzes the curvature sensing characteristics of this membrane-protein system, and elucidates key physical principles governing protein segregation on the wavy substrate and other in vitro systems. In this article we compute the local protein densities from the free energy landscape associated with membrane remodeling by curvature-inducing proteins. In specific, we use the Widom insertion technique to compute the free energy landscape for an inhomogeneous system with spatially varying density and the results obtained with this minimal model show excellent agreement with experimental studies that demonstrate the association between membrane curvature and local protein density. The free energy-based framework employed in this study can be used for different membrane morphologies and varied protein characteristics to gain mechanistic insights into protein sorting on membranes.
诱导曲率的蛋白参与细胞内的多种膜重塑过程。一些体外实验已经在模型脂质系统中定量了这些蛋白的曲率感应行为。其中一个系统由铺在波状基底上的双层膜组成（Hsieh 在 Langmuir 28:12838-12843, 2012）。在这些实验中，双层膜顺应波状基底，诱导曲率的蛋白在波状膜上表现出优先分离。利用基于 Helfrich 哈密顿量的介观计算膜模型，我们在这里进行了一项研究，分析了这种膜-蛋白系统的曲率感应特性，并阐明了控制蛋白在波状基底和其他体外系统中分离的关键物理原理。在本文中，我们通过曲率诱导蛋白的膜重构来计算与自由能景观相关的局部蛋白密度。具体来说，我们使用 Widom 插入技术来计算具有空间变化密度的非均匀系统的自由能景观，并且该最小模型的结果与实验研究非常吻合，实验研究证明了膜曲率与局部蛋白密度之间的关联。本研究中使用的基于自由能的框架可用于不同的膜形态和不同的蛋白特性，以深入了解蛋白在膜上的分类。
