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.

1034569Parikhthis提案测试了一个观念，即拓制性提示的动态表示可以触发曲率依赖的空间组织，并在受支持的脂质双层中进行重塑。在生物膜中，双层曲率不是细胞活性的被动结果。相反，它代表了一个主动构象转换，可以在空间上调节许多细胞表面相互作用和细胞内运输。尽管它们的重要性，但模型膜构型提供了静态和动态曲率的控制范围稀疏。这项工作的重点是设计和采用模型膜构型，这些膜构型允许对纯粹基于脂质的，简单的膜环境中的曲率，组成和动力学之间的耦合进行基本研究，这主要是使用EPI和共核荧光，光学椭圆形和原子椭圆的常规定量应用组合的组合。一些实验还利用了傅立叶变换红外振动光谱和差异扫描量热法。提出的努力提高了由局部分子组织（例如化学成分）和膜物理特性（例如填料缺陷，相变特性和膜张力）定义的曲率基础概念。建议这种利基本地化了关键的物理化学相互作用，其相互作用会产生曲率特异性和“曲率 - 感应”功能。该作品开发并采用了两层模型膜构型的类别，将支持的脂质双层与（1）可切换地形弹性体基材和（2）平面胶体晶体基板相结合。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研究范围。目的集中在三个特定区域上：（1）依赖曲率的空间组织的基础和具有定义的分子形状的膜分子的相位分离，包括在植物囊体或细菌膜中发现的分子形状； （2）通过膜曲线的时间依赖引入的动态重新平衡和曲率生态位形成； （3）产生具有自发曲率和曲率在促进水溶性磷脂酶激活的作用的分子的膜重塑杂菌素酶作用。该提案有助于物理和生物科学之间快速增长的合作。它利用分子定义和在波纹表面模板上模板的超分子生物分子结构开始解决有关脂质双层中曲率，动力学和组成偶联的长期问题。该作品提出的工作以允许将研究与教育无缝整合的方式整合了材料科学，表面化学和生物物理学。它试图利用这一机会以多种方式进行更广泛的影响。首先，建议这项工作将成为开发个人和中心类型合作的基础，这些合作受益于理论和计算，生物科学和高分辨率光学工具的应用。其次，计划的研究活动将有助于推进基于物理科学的方法和定量方法来解决生物学上重要的问题。第三，提出的工作将被利用以开发工程生物学课程，重点是分子水平设计。四十五岁，该项目的推论组成部分，尤其是类囊体模拟膜，为学生提供了探索他们对知识产权发展的研究和/或能源和生物学之间的学术发展的机会。第五，这将有助于持续的努力将小组环境作为一个不同科学学科的熔炉。第六，它将通过本科生和代表性不足的群体的参与来增强外展活动。