MOLECULAR FACTORS IN BIOMEMBRANE THICKNESSES

描述(由申请人提供)：通常假设膜中的双层膜的厚度与仅由脂类制成的囊泡中的厚度相同。许多想法都基于这一观点，包括疏水性扫描以发现螺旋，蛋白质在膜之间进行分类的概念，以及关于纯脂的大量文献的基本原理。然而，几乎没有测量结果作为实际膜厚度的参照点。同样，很少有数据能告诉我们可以被认为是未受扰动的双层的天然膜的面积比例。我们的初步研究表明，最初建立在流体马赛克模型中的经典观点可能需要修正：蛋白质而不是脂质决定了膜的尺寸。结果是蛋白质和脂肪之间存在菌株，其含义将是令人着迷的探索。这项建议的主要主题是使用衍射来测量膜蛋白、磷脂和胆固醇对膜厚度的相互影响，建立这些组分在膜中心占据的面积的值，并使用结合生物化学和分子动力学模拟的模型系统来识别潜在的化学原理。

DESCRIPTION (provided by applicant): It is often assumed that bilayers in membranes have the thicknesses that they would have in vesicles made from the lipids alone. Many ideas rest on this view, including hydrophobicity scans to find helices, notions of protein sorting between membranes, and the rationale for the huge literature on pure lipids. Yet almost no measurements exist as points of reference for the thicknesses of actual membranes. Similarly, there are few data to inform us of the proportion of the area of a natural membrane that can be regarded as an unperturbed bilayer. Our preliminary studies suggest that the classical view, first established in the Fluid Mosaic Model, may be in need of revision: proteins rather than lipids set membrane dimensions. A consequence is that strain exists between protein and lipid, and the implications will be fascinating to explore. The principal themes of this proposal are to use diffraction to measure the mutual influences of membrane proteins, phospholipid and cholesterol on membrane thickness, to establish values for the areas occupied by these components at the membrane center, and to use model systems that combine biochemistry and molecular dynamics simulations to discern the underlying chemical principles.