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Collaborative Research: Electro-Mechanical Interactions in Biological Membranes

合作研究：生物膜中的机电相互作用

基本信息

批准号：
1931084
负责人：
Ashutosh Agrawal
金额：
$ 26.82万
依托单位：
University of Houston
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1931084&HistoricalAwards=false
关键词：
Collaborative Research Electro Mechanical Interactions

项目摘要

Lipid membranes form the envelope surrounding the interior of biological cells. These membranes exhibitunique mechanical and electrical properties that interact in such a way as to facilitate a wide range ofbiological processes. The structure of the lipid molecules that constitute these membranes imparts unusualmechanical behavior resembling that of liquid crystals, a phase of matter intermediate between conventionalsolids and liquids. Another basic feature of plasma membranes is a negatively charged inner layer of lipidmolecules. These charged lipids diffuse on the membrane surface in response to physical forces. In turn,charged lipids play a significant role in regulating the functionality of membrane-embedded proteinstructures. The objective of this project is to formulate and employ mathematical and computational modelsto investigate electro-mechanical interactions of lipid-protein systems. Insights gained from the project willlead to improved understanding of physical processes occurring at the cellular level. This in turn is expectedto enhance understanding of the mechanisms underlying lipid-associated diseases and the efficacy of drugtherapies. Thus, the project will promote the progress of fundamental science and advance nationalpriorities in the critical area of healthcare. The project combines expertise in various branches of physics,structural engineering and cellular biology. It will provide advanced training to a diverse group of studentsand thereby enhance U.S. global competitiveness by contributing to the establishment of a new generationof interdisciplinary scientists and engineers.This project will provide the mathematical framework to describe the fundamental interactions of chargedlipids and proteins in biological membranes. It will culminate in a predictive tool for the simulation of themicroscopic electromechanical interactions responsible for a host of cellular functions. Its novel featuresinclude the use of continuum theory and molecular dynamics modeling of the coupled interplay betweenmembrane deformation at the lipid-protein interfaces, diffusion of charged lipids and proteins, and thequantification of the role of electric fields on the behavior of the combined system. The derived frameworkwould also assist researchers in the mechanics and material science communities to model complex 2Dinterfaces.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

脂质膜形成包围生物细胞内部的包膜。这些膜具有独特的机械和电学性质，它们以这样一种方式相互作用，以促进广泛的生物过程。构成这些膜的脂质分子的结构赋予了不寻常的机械行为，类似于液晶，一种介于常规固体和液体之间的物质相。质膜的另一个基本特征是带负电荷的脂质分子内层。这些带电荷的脂质响应物理力在膜表面扩散。反过来，带电荷的脂质在调节膜包埋蛋白质结构的功能中起着重要作用。本计画的目标是建立并运用数学与计算模型来研究脂质-蛋白质系统的电-机械相互作用。从该项目中获得的见解将导致对细胞水平上发生的物理过程的更好理解。这反过来有望增强对脂质相关疾病的机制和药物治疗效果的理解。因此，该项目将促进基础科学的进步，并推进国家在医疗保健这一关键领域的优先事项。该项目结合了物理学、结构工程和细胞生物学各个分支的专业知识。它将为不同的学生群体提供高级培训，从而通过培养新一代跨学科的科学家和工程师来提高美国的全球竞争力。该项目将提供数学框架来描述生物膜中带电脂质和蛋白质的基本相互作用。它最终将成为一种预测工具，用于模拟负责细胞功能的微观机电相互作用。它的新特点包括使用连续介质理论和分子动力学模型的耦合相互作用betweenmembrane变形在脂质-蛋白质界面，带电荷的脂质和蛋白质的扩散，和thequantitative的作用电场的行为的组合系统。衍生的框架也将帮助力学和材料科学界的研究人员模拟复杂的二维界面。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。