Collaborative Proposal: Mathematical and experimental study of lipid bilayer shape and dynamics mediated by surfactants and proteins

合作提案：表面活性剂和蛋白质介导的脂质双层形状和动力学的数学和实验研究

• 批准号: 1224656
• 负责人: Shravan Veerapaneni
• 金额: $ 10.57万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1224656&HistoricalAwards=false
• 关键词: Collaborative; Proposal; Mathematical; experimental; study

The objective of this project is to investigate the fundamental mathematics and biophysics that underlie the equilibrium shape and dynamics of a lipid bilayer interacting with surfactants and proteins. The lipid bilayer is the main structural component of the elastic biological membranes that consist of different lipid species, and contain many kinds of proteins, and many other molecules such as cholesterols and surfactants. In addition, the biomembranes are asymmetric double leaflets coupled to a cytoskeleton that is crucial for cellular adaptation of different shapes and motility. It is now known that lipid composition may set limits to the possible shapes and deformations, while the actual shape of the cellular membrane depends on both the force (from the cytoskeleton, for example) and membrane-deforming proteins. Much progress has been made to uncover and decipher the mechanisms by which proteins can sense and/or induce membrane curvature. However, recent experiments have shown that interaction between lipid membranes and amphipathic molecules, such as surfactant and amphipathic peptides, also leads to changes in total membrane area, curvature and rigidity. No mathematical modeling of these effects have yet been obtained to help elucidate the asymmetry in the lipid bilayer due to surfactants and proteins, or how cells may utilize these mechanisms to perform diverse biological functions. This project aims to establish mathematical understanding of the roles of surfactants and proteins in causing the asymmetries in lipid double leaflets and their subsequent shape and dynamics. The particular focuses are on (1) surfactant-induced membrane area regulation and shape change, and (2) effects of transport, assembly, and organization of trans-membrane proteins on membrane shape and dynamics. In addition, the experiments (by Stone) will validate and refine the modeling approach (by Young), which will in turn facilitate the numerical simulation (by Veerapaneni) of the elastic lipid bilayer interacting with surfactant and protein. Results will help uncover the complex organization and interplay between proteins and lipid domains in cellular membranes. The theme of this project is the development and analysis of mathematical models of the interaction between lipid membranes and surfactant or protein over large spatial (microns) and long time (seconds to minutes) scales, which is difficult to achieve using state-of-the-art coarse-grained molecular dynamics simulations. Quantitative comparison between experiments, mathematical modeling, and numerical simulations will be conducted. Broader impacts of the research include the development of new mathematical models, numerical methods and complementary analysis and experiments that will be of benefit to scientists and engineers studying rafts dynamics as well as emerging applications in drug delivery, cellular adhesion, motility and mechanosensing. The concepts and methods described here go beyond the context of moving boundary dynamics mediated by an active species, and extend to other problems featuring reaction-diffusion of chemicals. The approach has the potential to be adapted to more complicated biological membranes that are similar from a mathematical point of view. The students involved in this project will receive valuable interdisciplinary training in a wide range of mathematics, biophysics and computer science.

本计画的目标是研究与表面活性剂及蛋白质交互作用之脂质双层之平衡形状与动力学的基础数学与生物物理。脂双层是弹性生物膜的主要结构成分，由不同种类的脂质组成，并含有多种蛋白质、胆固醇和表面活性剂等分子。此外，生物膜是与细胞骨架偶联的不对称双叶，这对于细胞适应不同的形状和运动性至关重要。 现在我们知道，脂质成分可能会限制可能的形状和变形，而细胞膜的实际形状取决于力（例如来自细胞骨架）和膜变形蛋白。已经取得了很大的进展，揭示和破译蛋白质可以感知和/或诱导膜曲率的机制。然而，最近的实验表明，脂膜和两亲分子之间的相互作用，如表面活性剂和两亲肽，也导致总膜面积，曲率和刚度的变化。尚未获得这些效应的数学模型来帮助阐明由于表面活性剂和蛋白质引起的脂质双层的不对称性，或者细胞如何利用这些机制来执行不同的生物功能。该项目旨在建立对表面活性剂和蛋白质在导致脂质双小叶及其随后的形状和动力学不对称性中的作用的数学理解。特别关注的是（1）表面活性剂诱导的膜面积调节和形状变化，（2）跨膜蛋白的运输，组装和组织对膜形状和动力学的影响。此外，实验（由斯通）将验证和完善建模方法（由杨），这反过来又将促进弹性脂质双层与表面活性剂和蛋白质相互作用的数值模拟（由Veerapaneni）。研究结果将有助于揭示细胞膜中蛋白质和脂质结构域之间的复杂组织和相互作用。 该项目的主题是在大空间（微米）和长时间（秒到分钟）尺度上开发和分析脂质膜与表面活性剂或蛋白质之间相互作用的数学模型，这是使用最先进的粗粒度分子动力学模拟难以实现的。实验，数学建模和数值模拟之间的定量比较将进行。该研究的更广泛影响包括开发新的数学模型，数值方法和补充分析和实验，这将有利于科学家和工程师研究筏动力学以及药物输送，细胞粘附，运动和机械传感的新兴应用。这里描述的概念和方法超越了由活性物质介导的移动边界动力学的背景，并扩展到其他具有化学品反应扩散特征的问题。 该方法有可能适用于从数学角度来看相似的更复杂的生物膜。参与该项目的学生将在广泛的数学，生物物理学和计算机科学方面接受宝贵的跨学科培训。