MOLECULAR FACTORS IN BIOMEMBRANE THICKNESSES

描述（由申请人提供）：通常认为膜中的双层具有单独由脂质制成的囊泡中的厚度。许多想法都建立在这一观点之上，包括寻找螺旋的疏水性扫描，膜之间蛋白质分选的概念，以及关于纯脂质的大量文献的基本原理。然而，几乎没有测量存在作为实际膜厚度的参考点。同样，很少有数据告诉我们，天然膜的面积的比例，可以视为一个未受干扰的双分子层。我们的初步研究表明，首先在流体镶嵌模型中建立的经典观点可能需要修正：蛋白质而不是脂质决定膜的尺寸。结果是，在蛋白质和脂质之间存在张力，其影响将是令人着迷的探索。本提案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，建立这些成分在膜中心占据的区域的值，并使用结合生物化学和分子动力学模拟的模型系统来辨别潜在的化学原理。

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.