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.

1034569 Parikh该提案测试了拓扑化学线索的动态呈现可以触发支持的脂质双层中的曲率依赖性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，它代表了一个积极的构象转换空间调节许多细胞表面的相互作用和细胞内运输。尽管它们的重要性，模型膜配置，提供控制引入静态和动态曲率是稀疏的。这项工作的重点是设计和采用模型膜配置，允许基本的调查之间的耦合曲率，成分和动力学在纯脂质为基础的，简单的膜环境主要使用常规定量应用的组合的epi和共聚焦荧光，光学椭圆偏振，和原子力显微镜。有些实验还利用傅里叶变换红外振动光谱和差示扫描量热法。所提出的努力推进了由局部分子组织定义的曲率生态位的概念（例如，化学组成）和膜物理性质（例如，填充缺陷、相变性质和膜张力）。这个利基，它建议，本地化的相互作用产生曲率特异性和“曲率传感”能力的关键物理化学相互作用。这项工作开发并采用了两种平行的模型膜配置，将支持的脂质双层与（1）可切换的地形弹性体基板和（2）平面胶体晶体基板集成在一起。这些平台的通用性质提供了曲率依赖性膜组织，重塑及其功能后果的生物物理学研究的范围。其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的相分离的基础，具有确定的分子形状，包括那些在植物类囊体或细菌膜中发现的分子;（2）动态再平衡和曲率生态位的形成，通过时间依赖的膜曲率的引入;和（3）通过磷脂酶作用的膜重塑，其产生具有自发弯曲的分子，以及弯曲在促进水溶性磷脂酶的活化中的作用。这一建议有助于物理科学和生物科学之间迅速增长的合作。它利用分子定义和超分子生物分子结构的模板在波纹表面开始，以解决长期存在的问题，关于耦合的曲率，动力学，和组合物的脂质双层。这项工作将材料科学、表面化学和生物物理学结合在一起，使研究与教育无缝结合。它寻求利用这个机会以多种方式产生更广泛的影响。首先，它建议的努力将作为一个基地，发展个人和中心类型的合作，受益于并行的努力，在理论和计算，生物科学，高分辨率光学工具的应用。第二，计划中的研究活动将有助于促进使用基于物理科学的方法和定量方法来解决生物学上的重要问题。第三，本研究将用于开发工程生物学课程，重点是分子水平的设计。第四，本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发展和/或在能源和生物学之间发展学术重点的机会。第五，它将有助于将团队环境建设成为不同科学学科的熔炉。第六，它将通过大学生和代表性不足的群体的参与加强外联活动。