Curvature-dependent Lipid Organization at Surfaces

表面曲率依赖性脂质组织

• 批准号: 1034569
• 负责人: Atul Parikh
• 金额: $ 22.5万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1034569&HistoricalAwards=false
• 关键词: Curvature; dependent; Lipid; Organization; Surfaces

1034569ParikhThis proposal tests the notion that dynamic presentation of topochemical cues can trigger curvature-dependent spatial organization and remodeling in supported lipid bilayers. In biological membranes, bilayer curvature is not a passive consequence of cellular activity. Rather it represents an active conformational switch to spatially regulate many cell surface interactions and intracellular trafficking. Despite their importance, model membrane configurations that afford controlled introduction of static and dynamic curvatures are sparse. The effort is focused on devising and employing model membrane configurations that allow fundamental investigations of couplings between curvature, composition, and dynamics in purely lipid based, simple membrane environments primarily using a combination of routine quantitative applications of epi and confocal fluorescence, optical ellipsometric, and atomic force microscopies. Some experiments also utilize Fourier transform infrared vibrational spectroscopy and differential scanning calorimetry.Intellectual Merit. The effort proposed advances the concept of curvature-niche defined by the local molecular organization (e.g., chemical composition) and membrane physical properties (e.g., packing defects, phase transition properties, and membrane tension). This niche, it is suggested, localizes key physical chemical interactions whose interplay produces curvature specificity and "curvature-sensing" capabilities. The work develops and employs twoparallel classes of model membrane configuration that integrate supported lipid bilayers with (1)switchable topography elastomeric substrates and (2) planar colloidal crystal substrates. The generic nature of these platforms affords the range of biophysical studies of curvature dependent membrane organization, remodeling, and their functional consequences. The aims are focused on three specific areas: (1) the basis for curvature dependent spatial organization and phase separation of membrane molecules with defined molecular shapes including those found in plant thylakoid or bacterial membranes; (2) dynamic re-equilibration and curvature niche formation via time dependent introduction of membrane curvatures; and (3) membrane remodeling viasphingomyelinase action which generates molecules with spontaneous curvature and role of curvatures in promoting activation of a water soluble phospholipase enzyme.Broader Impact. This proposal contributes to the rapidly growing collaboration between physical and biological sciences. It takes advantage of molecular definition and supramolecular biomolecular structures templated at corrugated surfaces to begin to address long standing questions regarding the coupling of curvature, dynamics, and composition in lipid bilayers. The work proposed integrates materials science, surface chemistry, and biophysics in a manner that allows a seamless integration of research with education. It seeks to exploit this opportunity for broader impact in multiple ways. First, it is suggested that the effort will serve as a base for developing individual and center type collaborations that benefit from parallel efforts in theory andcomputations, biological sciences, and applications of high resolution optical tools. Second, the research activities planned will help advance the use of physical science based approaches and quantitative methods to addressing biologically important problems. Third, the work proposed will be leveraged to develop a course in engineering biology with a focus on molecular level design.Fourth, the corollary components of the project, in particular thylakoid-mimetic membranes, offer students opportunities to explore their research toward intellectual property development and/or develop an academic focus between energy and biology. Fifth, it will help ongoing efforts inbuilding the group environment as a melting pot of disparate scientific disciplines. Sixth, it will enhance outreach activities by the involvement of undergraduate students and underrepresented groups.

[34569]这一提议验证了拓扑化学线索的动态呈现可以触发支持的脂质双层中曲率依赖的空间组织和重塑的概念。在生物膜中，双层曲率不是细胞活动的被动结果。相反，它代表了一种主动的构象转换，在空间上调节许多细胞表面相互作用和细胞内运输。尽管它们很重要，但能提供静态和动态曲率可控引入的模型膜结构是稀疏的。这项工作的重点是设计和采用模型膜结构，允许在纯脂基、简单膜环境中对曲率、组成和动力学之间的耦合进行基本研究，主要使用常规定量应用的组合，包括外延显微镜和共聚焦荧光、光学椭差和原子力显微镜。一些实验还使用傅里叶变换红外振动光谱法和差示扫描量热法。知识价值。提出的努力推进了曲率生态位的概念，曲率生态位由局部分子组织（例如，化学成分）和膜物理性质（例如，包装缺陷，相变性质和膜张力）定义。研究人员认为，这个生态位定位了关键的物理化学相互作用，这些相互作用产生了曲率特异性和“曲率感应”能力。这项工作开发并采用了两种平行的模型膜结构，将支持的脂质双层与(1)可切换的地形弹性体基质和(2)平面胶体晶体基质结合在一起。这些平台的通用性质提供了曲率依赖膜组织、重塑及其功能后果的生物物理研究范围。目标集中在三个特定领域：(1)曲率依赖的空间组织和膜分子相分离的基础，具有确定的分子形状，包括在植物类囊体或细菌膜中发现的分子；(2)膜曲率随时间引入的动态再平衡和曲率生态位形成；(3)膜重塑，产生具有自发曲率的分子，以及曲率在促进水溶性磷脂酶活化中的作用。更广泛的影响。这一建议有助于物理科学和生物科学之间迅速发展的合作。它利用分子定义和在波纹表面模板化的超分子生物分子结构，开始解决长期存在的关于曲率、动力学和脂质双层组成耦合的问题。这项工作将材料科学、表面化学和生物物理学结合起来，使研究与教育无缝结合。它寻求利用这一机会，以多种方式产生更广泛的影响。首先，建议这项工作将作为发展个人和中心类型合作的基础，这些合作将受益于理论和计算、生物科学和高分辨率光学工具应用方面的并行努力。其次，计划的研究活动将有助于促进基于物理科学的方法和定量方法的使用，以解决生物学重要问题。第三，所提出的工作将被用于开发一门以分子水平设计为重点的工程生物学课程。第四，项目的必然组成部分，特别是类囊体模拟膜，为学生提供了探索知识产权开发和/或在能源和生物学之间发展学术重点的机会。第五，它将有助于正在进行的努力，将群体环境建设为不同科学学科的大熔炉。第六，它将通过本科生和代表性不足的群体的参与来加强外展活动。