Theoretical Approach to Organization and Function of Biological Membranes

生物膜组织和功能的理论方法

• 批准号: 0803956
• 负责人: Michael Schick
• 金额: $ 31.2万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0803956&HistoricalAwards=false
• 关键词: Theoretical; Approach; Organization; Function; Biological

TECHNICAL SUMMARY:This award supports theoretical research and education in biological physics. The research involves a series of increasingly sophisticated models of biological membranes which are designed to elucidate salient structure in the organization of molecules in the membrane. This idea, that molecules in the membrane of a cell are not distributed uniformly, underlies a set of new research questions. The underlying hypothesis is that the distribution of proteins and other molecules, such as cholesterol, in the cell membrane leads to functional organization, i.e. this organization can affect a host of other biologically important processes such as cell signaling, membrane fusion, viral entry and a variety of other functions which involve the cell membrane. Techniques of statistical mechanics and simulation will be used to explicate behaviors of model bilayer membranes consisting of cholesterol, saturated and unsaturated lipids with specific goal of observing the phase separation in this quasi-two dimensional fluid. Three specific phenomenon are highlighted in this research. The first attempts to identify sound theoretical basis for the existence (or nonexistence) and properties and dynamics of membrane rafts. Such rafts, described as regions of saturated lipids and cholesterol that had aggregated and float together. The functionality which is associated with rafts derives from the attachment of signaling proteins to the edges of the raft and thereby providing structural organization for signaling processes the couple the interior and exterior of the cell. NON-TECHNICAL SUMMARY:This award supports fundamental theoretical research and education on the biological physics of cell membranes. Scientific understanding of living cells has clearly shown that the cell membrane is complex and sophisticated in its functionality, doing far more than simply acting as a container holding the contents of the cell in place. With new understanding that the molecules that form the membrane are not entirely disorganized, there have developed a number of conjectures of how the intrinsic structure in a cell membrane may organize the way biological processes occur in the region where transport of signaling occur between the cell interior and its external environment. The research will employ tools of theoretical physics and use computer simulations to describe the organization of molecules in groups in the membrane. These tools allow researchers to establish what sort of structures can exist in the membrane and whether this pays an essential role in allowing the cell to carry out the essential life processes. A key concept of cell membrane organization is that the membrane includes floating groups of molecules which carry specialized signaling molecules or other proteins involved in allowing the cell to communicate with its environment.This research will be conducted with the full participation of graduate students, who will be trained in modern methods of theory and computer simulation as applicable to biological systems, preparing them for careers in science and biotechnology. Finally the research will be performed in collaboration with scientists from the US and abroad, strengthening and enriching the US physical community.

技术综述：该奖项支持生物物理的理论研究和教育。这项研究涉及一系列日益复杂的生物膜模型，旨在阐明膜中分子组织的显著结构。这种认为细胞膜上的分子不是均匀分布的观点，构成了一系列新的研究问题的基础。基本的假设是，蛋白质和其他分子，如胆固醇，在细胞膜上的分布导致功能组织，即这种组织可以影响许多其他生物学上重要的过程，如细胞信号、膜融合、病毒进入和涉及细胞膜的各种其他功能。我们将利用统计力学和模拟技术来解释由胆固醇、饱和和不饱和脂类组成的模型双层膜的行为，目的是观察这种准二维流体中的相分离。本研究突出了三个具体现象。第一个尝试确定膜筏存在(或不存在)、特性和动力学的可靠的理论基础。这类木筏被描述为聚集在一起并漂浮在一起的饱和脂肪和胆固醇的区域。与木筏相关的功能来自于信号蛋白附着在木筏的边缘，从而为连接细胞内部和外部的信号过程提供结构组织。非技术概述：该奖项支持细胞膜生物物理的基础理论研究和教育。对活细胞的科学理解清楚地表明，细胞膜在功能上是复杂和复杂的，它所做的远远不止是简单地充当一个容器，将细胞的内容物保持在适当的位置。随着对形成膜的分子并不是完全无序的新理解，人们提出了许多猜测，即细胞膜的内在结构如何组织发生在细胞内部和外部环境之间信号传输的区域中发生的生物过程。这项研究将使用理论物理工具，并使用计算机模拟来描述膜中分子的群组组织。这些工具使研究人员能够确定细胞膜中可以存在什么样的结构，以及这是否在允许细胞进行必要的生命过程方面发挥了重要作用。细胞膜组织的一个关键概念是，细胞膜包括漂浮的分子基团，这些分子携带特殊的信号分子或其他蛋白质，参与细胞与环境的交流。这项研究将由研究生全面参与，他们将接受适用于生物系统的现代理论和计算机模拟方法的培训，为他们在科学和生物技术领域的职业生涯做准备。最后，这项研究将与来自美国和国外的科学家合作进行，加强和丰富美国物理界。