The Viscosity of Lipid and Protein Membranes

脂质和蛋白质膜的粘度

• 批准号: 1507115
• 负责人: Raghuveer Parthasarathy
• 金额: $ 36万
• 依托单位: University of Oregon Eugene
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1507115&HistoricalAwards=false
• 关键词: Viscosity; Lipid; Protein; Membranes

Non-technical: This award by the Biomaterials program in the Division of Materials Research to University of Oregon is to apply recently developed methods for measuring membrane fluidity to several basic issues involving the nature of two-dimensional flows in membranes, the relationships between viscosity and membrane tension, and the dependence of viscosity on lipid structure. Membranes are critical components of all living cells that provide a flexible framework in which lipids and proteins build structures, perform chemical reactions, and spatially reorganize. These tasks are made possible by the physical properties of the lipid bilayer, the two-molecule-thick structure that forms the basis of all cellular membranes. The two-dimensional fluidity of lipid bilayers is essential to their function, as it enables the mobility of membrane molecules. Characterization of bilayer viscosity, however, remains minimal, which limits our ability to develop quantitative, predictive models of important processes such as intracellular cargo trafficking and signal transduction. The proposed experiments will also enhance educational and outreach activities. For example, discussions of membrane behavior and biophysical modes of inquiry will illuminate a course for non-science majors developed by the PI that explores the physical properties of organisms and biological materials, with the broad aim of promoting scientific literacy. Regarding outreach, the PI initiated and co-runs a week long Physics Day Camp for high school students from low socioeconomic backgrounds that provides an exposure to science as well as, more broadly, a greater familiarity with the nature of higher education. The PI and his group lead activities related to biomaterials and microscopy. These studies also provide opportunities for training undergraduates and graduate students in methods of membrane biophysics, optics, and computational image analysis. Technical: The two-dimensional fluidity of cellular membranes is essential to their function, as it enables the mobility of constituent lipids and proteins as well as the spatial reorganization of lipid domains, protein complexes, and other larger-scale structures. Though the existence and importance of membrane fluidity are well established, characterizations of the material properties underlying it remain crude. Specifically, the viscosity of lipid bilayers has proven challenging to measure due to membranes' fragility and small size, and also due to the intrinsic complexity of two-dimensional hydrodynamics. Our incomplete understanding of membrane viscosity frustrates models of membrane dynamics. In the proposed experiments, the investigator will build on techniques that have recently developed in making use of both single- and two-point rheological approaches to address various fundamental questions of membrane biophysics. The researcher will examine whether standard hydrodynamic models are applicable at short length scales, where they have not been rigorously tested. Relationships between viscosity and membrane tension, and between viscosity and out-of-plane fluctuations will also will be studies with this project. The dependence of lipid bilayer viscosity on acyl chain length, temperature, the presence of proteins that insert into the bilayer, and the density of membrane inclusions, all of which will provide a rich picture of membrane material properties will be characterized with this research study. The proposed studies will impact educational work, most notably related to a general education biophysics course for non-science majors, outreach work, related especially to a day camp for high school students from low socioeconomic backgrounds, and training of students in a range of methods related to membrane biophysics, optics, and computational image analysis.

非技术性：俄勒冈大学材料研究部生物材料计划授予俄勒冈大学的这一奖项是将最近开发的测量膜流动性的方法应用于几个基本问题，涉及膜中二维流动的性质、粘度与膜张力之间的关系以及粘度与脂质结构的相关性。膜是所有活细胞的关键组成部分，它为脂质和蛋白质构建结构、执行化学反应和空间重组提供了一个灵活的框架。这些任务是由脂质双层的物理性质实现的，这种两个分子厚的结构构成了所有细胞膜的基础。脂质双层的二维流动性对其功能至关重要，因为它使膜分子的流动性成为可能。然而，双层粘度的表征仍然很少，这限制了我们开发重要过程的定量、预测模型的能力，如细胞内货物运输和信号转导。拟议的实验还将加强教育和外联活动。例如，关于膜行为和生物物理探究模式的讨论将说明由PI为非科学专业开发的一门课程，该课程探索生物体和生物材料的物理性质，其广泛目的是促进科学素养。在外展方面，国际和平协会为社会经济背景较低的高中生发起并共同开办了为期一周的物理日营，让他们有机会接触科学，更广泛地说，让他们更熟悉高等教育的性质。PI和他的团队领导着与生物材料和显微镜相关的活动。这些研究还为本科生和研究生提供了培训膜生物物理学、光学和计算图像分析方法的机会。技术：细胞膜的二维流动性对其功能至关重要，因为它使组成脂类和蛋白质的流动性以及类脂域、蛋白质复合体和其他更大规模结构的空间重组成为可能。尽管膜流动性的存在和重要性已经得到了很好的证实，但对其背后的材料性质的表征仍然很粗糙。具体地说，由于膜的脆性和小尺寸，以及二维流体动力学的内在复杂性，脂双层的粘度被证明是具有挑战性的测量。我们对膜粘度的不完全理解阻碍了膜动力学模型的建立。在拟议的实验中，研究人员将建立在最近开发的技术的基础上，利用单点和两点流变学方法来解决膜生物物理的各种基本问题。研究人员将检查标准流体动力学模型是否适用于未经过严格测试的短尺度。这个项目还将研究粘度和膜张力之间的关系，以及粘度和平面外波动之间的关系。脂双层粘度与酰基链长、温度、插入双层的蛋白质的存在以及膜包涵体的密度的关系将通过这项研究来表征，所有这些都将为膜材料的性质提供丰富的图景。拟议的研究将影响教育工作，最主要的是与非理科专业的普通教育生物物理学课程有关，推广工作，特别是与社会经济背景较低的高中生日营有关的推广工作，以及对学生进行与膜生物物理、光学和计算图像分析相关的一系列方法的培训。