Nano-elasticity of lipid membranes: continuum theory, molecular-level simulations, and application to dynamin-induced membrane fission

来自卡内基梅隆大学的Markus Rumonno得到了化学系化学理论，模型和计算方法项目的支持，以开发非常小规模的脂质膜预测理论和计算模型。材料研究部的凝聚态物质和材料理论计划也有助于获得该奖项。 脂质膜是所有活细胞的主要结构组成部分。它们将细胞从其环境中分离出来，并经常将细胞分成更小的专门区室，称为“细胞器”。在分裂的细胞中，细胞膜呈现出各种各样复杂的形状。虽然研究人员有很好的理论和计算模型来描述一些形状，但其他形状却不太清楚，尽管这些形状可能在细胞过程中起着关键作用。Alberno教授和他的研究小组正在开发更好的理论来理解脂质膜的形状以及它如何影响细胞功能。此外，该项目通过提供本科和研究生课程（统计热力学，生物物理学）的课堂和家庭作业材料的许多示例以及理论或计算建模教程的教学指导性脚本来促进学习。该主题为富有成效的本科生研究项目提供了机会。 特别努力吸引少数民族学生到科学利用推广项目与初中和高中在匹兹堡。 演示材料由日常材料制成，如纸和塑料箔。定量操作这些材料的能力引导学生从直观熟悉的机械稳定性的想法，适用于建筑物和桥梁，他们意想不到的应用在细胞生物学？该奖项支持理论和计算研究和教育，以改善纳米尺度下脂质膜弹性的定量描述。该项目旨在将膜曲率和脂质倾斜之间的经典耦合扩展到双二阶，为理解许多新的细胞生物学现象打开大门。 该研究小组用广泛的计算和实验数据库来面对精炼的理论，以彻底测试理论并提取进一步预测所需的潜在弹性参数。 研究人员扩展了理论框架，以涵盖具有挑战性但生物学上常见的膜情况，这些膜不仅由脂质混合物组成，而且其组成可能在两个膜小叶之间存在差异（不对称膜）。 最后，该团队预测了涌现的膜特性，如边缘张力或裂变屏障，或者更一般地说，涉及高度弯曲区域的情况，这些区域将目前的弹性膜理论推到了极限之外。作为一个特别重要的应用，膜裂变的过程正在研究通过理论和粗粒度的计算建模相结合。这项工作阐明了脂质膜和封闭的动力蛋白丝之间的应力，破坏平衡的末端效应的重要性，热波动的作用;以及主动收缩的后果。该奖项反映了NSF的法定使命，并被认为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来支持。

Markus Deserno from Carnegie Mellon University is supported by the Chemical Theory, Models and Computational Methods Program in the Division of Chemistry to develop predictive theoretical and computational models for lipid membranes at very small scales. The Condensed Matter and Materials Theory Program in the Division of Materials Research also contributes to this award. Lipid membranes are a major structural components of all living cells. They separate a cell from its environment and often divide cells into smaller specialized compartments, called "organelles". In dividing cells, membranes assume a great variety of intricately shapes. While researchers have excellent theoretical and computational models to describe some shapes, others are less well understood, even though these shapes may have key roles in cellular processes. Professor Deserno and his research group are developing better theories for understanding the shapes of lipid membranes and how this affects the cell function. Furthermore, this project advances learning, by providing many examplesfor classroom and homework material in both undergraduate and graduate courses (statistical thermodynamics, biological physics), as well as pedagogically-instructive scripts for theoretical or computational modeling tutorials. The topic offers opportunities for productive undergraduate research projects. Special efforts are made to attract minority students to science using outreach projects with both middle and high schools in Pittsburgh. Demonstration materials are made of everyday materials such as paper and plastic foils. The ability to manipulate such materials quantitatively guide students from intuitively-familiar ideas about mechanical stability, as applied to buildings and bridges, to their unexpected applications in cell biology?related to understanding the human body.This award supports theoretical and computational research and education to improve the quantitative description of lipid membrane elasticity at the nanoscale. The project seeks to extend the classical coupling between membrane curvature and lipid tilt to biquadratic order, opening the door to understanding numerous new cell biology phenomena. The research group confronts the refined theory with a broad repertoire of computational and experimental data, to thoroughly test the theory and extract underlying elastic parameters needed for further predictions. The researchers extend the theoretical framework to encompass the challenging but biologically common situation of membranes that not only consists of a mixture of lipids, but whose composition might differ between the two membrane leaflets (asymmetric membranes). Finally, the team predicts emergent membrane properties such as edge tensions or fission barriers, or more generally, situations involving highly curved regions that push present elastic membrane theories beyond their limits. As an especially important application, the process of membrane fission is being studied through a combination of theoretical and coarse-grained computational modeling. This work is elucidating the stresses between the lipid membrane and the enclosing dynamin filament, the importance of symmetry-breaking end-effects, and the role of thermal fluctuations; and the consequence of active constriction.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.