Computational Investigations of Compositional Heterogeneities in Lipid Membranes

脂质膜成分异质性的计算研究

• 批准号: 0812470
• 负责人: Mohamed Laradji
• 金额: $ 20万
• 依托单位: University of Memphis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0812470&HistoricalAwards=false
• 关键词: Computational; Investigations; Compositional; Heterogeneities; Lipid

TECHNICAL ABSTRACT:This award supports theoretical research and education in the study of nanoscale heterogeneities in biological membranes, so called ''rafts''. Research on these lateral heterogeneities in biomembranes is motivated by a need to know their physiological and structural functions. The is extensive research indicating that mammalian cells exhibit compositional heterogeneities in the form of small domains, called rafts, with diameter ranging between 50 and 200 nm. Lipid rafts are believed to be highly dynamic, rich in sphingolipids, which are mainly saturated lipids, and cholesterol. Lipid rafts are also believed to play a role in a variety of physiological functions including protein trafficking, lipid sorting, signal transduction, and endocytosis. There are striking questions raised when studying living biological systems in comparison to synthetic membrane. Numerous experiments on synthetic lipid membranes, demonstrated the existence of domains, thus supporting the raft model in biomembranes. However, lipid rafts in biomembranes, which are nanoscale in size, are orders of magnitude smaller than the lipid domains in synthetic membranes. The present research investigates raft formation and dynamics of membrane heterogeneities through systematic and large scale mesoscale numerical simulations. Computer simulations allow the study of phase behavior of multicomponent membranes and investigate possible mechanisms leading to the stability of nanoscale lipid rafts in biomembranes. Using coarse-grained molecular dynamics (CGMD) simulations of a recently developed model, the PI will investigate the phase behavior of ternary lipid mixtures composed of a saturated lipid, an unsaturated lipid and cholesterol, with a particular focus on the two-phase liquid-liquid coexistence, which is relevant to the lipid rafts in biomembranes. A more coarse-grained model based on soft-core interactions will be developed for self assembled amphiphiles and will be used to investigate three-component lipid membranes in the two-phase liquid-liquid coexistence. The model will be used in conjunction with a hybrid approach combining dissipative particle dynamics (DPD) with semi-grand canonical Monte Carlo technique. Beyond the basic research, the award has educational implications and potential broader impact in other areas. Due to its multidisciplinary nature, the research will have a broad impact on both the physical and life sciences. Graduate and undergraduate students are involved in this research. The computational nature of this proposed research makes it particularly accessible to undergraduate students. This research will also benefit the new Computational Physics Concentration at the University of Memphis. The research will be integrated with the current educational agenda of the University of Memphis which has a significant minority student population. The senior undergraduate biophysics course and the graduate computational course at the University of Memphis benefit from this program by the proximity of an active research program which can relate the character of research activities in this area. The PI is also teaming up with other faculty members at the physics department to create a high school physics internship program in which a number of students will be selected every year from the Memphis area high schools and will be involved in research experience projects.NONTECHNICAL ABSTRACT:This award supports theoretical research and education in the study of molecular clustering in biological membranes, so called ''rafts''. Research on these molecular groupings in biomembranes is motivated by a need to know their physiological and structural functions. The is extensive research indicating that all animal cells form these small domains, called rafts, with small diameter of around 1/100th the size of the cell. Lipid rafts are believed to be highly dynamic and mainly saturated lipids, and cholesterol. Lipid rafts are also believed to play a role in a variety of physiological functions, including transfer of materials into and out of a cell. There are striking questions raised when studying living biological systems in comparison to synthetic membrane. Numerous experiments on synthetic lipid membranes, demonstrated the existence of domains, thus supporting the raft model in biomembranes. However, lipid rafts in biomembranes are a hundred times smaller than the lipid domains in synthetic membranes. This is only one aspect of rafts that is investigated in this research. The present research investigates raft formation and dynamics of membrane composition through systematic and large scale numerical simulations. Computer simulations allow the study of membrane composition and investigate possible mechanisms leading to the stability of lipid rafts. Beyond the basic research, the award has educational implications and potential broader impact in other areas. Due to its multidisciplinary nature, the research will have a broad impact on both the physical and life sciences. Graduate and undergraduate students are involved in this research. The computational nature of this proposed research makes it particularly accessible to undergraduate students. This research will also benefit the new Computational Physics Concentration at the University of Memphis. The research will be integrated with the current educational agenda of the University of Memphis which has a significant minority student population. The senior undergraduate biophysics course and the graduate computational course at the University of Memphis benefit from this program by the proximity of an active research program which can relate the character of research activities in this area. The PI is also teaming up with other faculty members at the physics department to create a high school physics internship program in which a number of students will be selected every year from the Memphis area high schools and will be involved in research experience projects.

技术摘要：该奖项支持理论研究和教育在生物膜中纳米级异质性研究中，所谓的“木筏”。关于生物膜中这些侧向异质性的研究是出于了解其生理和结构功能的需要。 这项广泛的研究表明，哺乳动物细胞以小域的形式表现出组成异质性，称为木筏，直径在50至200 nm之间。据信脂质筏具有高度动态性，富含鞘脂，主要是饱和脂质和胆固醇。脂质筏还被认为在多种生理功能中发挥作用，包括蛋白质运输，脂质排序，信号转导和内吞作用。 与合成膜相比，研究生物系统时提出了一个明显的问题。关于合成脂质膜的许多实验证明了结构域的存在，因此支持了生物膜中的筏模型。然而，生物膜中的脂质筏的大小是纳米级的，比合成膜中的脂质结构域小的数量级。本研究通过系统和大规模的中尺度数值模拟研究了膜异质性的筏形成和动力学。计算机模拟允许研究多组分膜的相行为，并研究可能导致纳米级脂质筏在生物膜中稳定性的机制。使用最近开发的模型的粗粒分子动力学（CGMD）模拟，PI将研究由饱和脂质，不饱和脂质和胆固醇组成的三元脂质混合物的相位行为，特别关注两相液体液体的共有性，与脂质液体相关，这与脂质含量相关。基于软核相互作用的更粗粒的模型将用于自组装的两亲物，并将用于研究两相液 - 液体共存中的三组分脂质膜。该模型将与将耗散粒子动力学（DPD）与半宏观规范蒙特卡洛技术结合的混合方法结合使用。除了基础研究之外，该奖项还具有教育意义和对其他领域的潜在更广泛的影响。由于其多学科性质，该研究将对物理科学和生命科学产生广泛的影响。研究生和本科生参与了这项研究。这项拟议的研究的计算性质使本科生特别可以使用。这项研究还将使孟菲斯大学的新计算物理集中度受益。这项研究将与孟菲斯大学的当前教育议程融合，该议程具有少数族裔学生群体。孟菲斯大学的高级本科生物物理学课程和毕业生计算课程通过该计划的距离受益于该计划，该计划的活动可以与该领域的研究活动联系起来。 PI还与物理系的其他教职员工合作，创建了一个高中物理实习计划，该计划每年将从孟菲斯地区高中选出许多学生，并将参与研究经验项目。NOntechnical摘要：该奖项支持理论研究和在生物膜中的分子聚类研究中的理论研究和教育。关于生物膜中这些分子组的研究是出于需要了解其生理和结构功能的动机。 这项广泛的研究表明，所有动物细胞都形成了这些小域，称为筏，小直径约为细胞大小的1/100。脂肪筏被认为是高度动态的，主要是饱和脂质和胆固醇。脂质筏还被认为在多种生理功能中起作用，包括将材料转移到细胞中。与合成膜相比，研究生物系统时提出了一个明显的问题。关于合成脂质膜的许多实验证明了结构域的存在，因此支持了生物膜中的筏模型。然而，生物膜中的脂质筏比合成膜中的脂质结构域小100倍。 这只是这项研究中正在研究的筏子的一个方面。本研究通过系统和大规模的数值模拟研究了膜组成的筏形成和动力学。计算机模拟允许研究膜组成并研究导致脂质筏稳定性的可能机制。除了基础研究之外，该奖项还具有教育意义和对其他领域的潜在更广泛的影响。由于其多学科性质，该研究将对物理科学和生命科学产生广泛的影响。研究生和本科生参与了这项研究。这项拟议的研究的计算性质使本科生特别可以使用。这项研究还将使孟菲斯大学的新计算物理集中度受益。这项研究将与孟菲斯大学的当前教育议程融合，该议程具有少数族裔学生群体。孟菲斯大学的高级本科生物物理学课程和毕业生计算课程通过该计划的距离受益于该计划，该计划的活动可以与该领域的研究活动联系起来。 PI还与物理系的其他教职员工合作，创建了一个高中物理实习计划，其中每年将从孟菲斯地区高中选出许多学生，并将参与研究经验项目。