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

卡内基梅隆大学的Markus Deserno在化学系化学理论、模型和计算方法项目的支持下，开发了非常小尺度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项目也为该奖项做出了贡献。脂质膜是所有活细胞的主要结构成分。它们将细胞从环境中分离出来，并经常将细胞分裂成更小的特殊隔间，称为“细胞器”。在细胞分裂过程中，细胞膜呈现出各种复杂的形状。虽然研究人员有很好的理论和计算模型来描述一些形状，但其他的形状还不太清楚，尽管这些形状可能在细胞过程中起着关键作用。德瑟诺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及其如何影响细胞功能。此外，该项目通过为本科和研究生课程（统计热力学、生物物理学）的课堂和家庭作业材料提供许多例子，以及为理论或计算建模教程提供教学指导脚本，促进了学习。该主题为富有成效的本科生研究项目提供了机会。通过与匹兹堡的初中和高中开展外展项目，为吸引少数民族学生学习科学做出了特别努力。演示材料由日常材料制成，如纸和塑料箔。对这些材料进行定量操作的能力将引导学生从直觉上熟悉的机械稳定性概念，如应用于建筑物和桥梁，到它们在细胞生物学中的意想不到的应用。与了解人体有关。该奖项支持理论和计算研究和教育，以改善纳米尺度上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次阶，为理解许多新的细胞生物学现象打开大门。研究小组用广泛的计算和实验数据来面对精炼的理论，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，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不同（不对称膜）。最后，该团队预测了诸如边缘张力或裂变障碍之类的紧急膜特性，或者更一般地说，涉及高度弯曲区域的情况，这些情况将现有的弹性膜理论推向极限。作为一个特别重要的应用，膜裂变的过程正在通过理论和粗粒度计算模型相结合的方式进行研究。这项工作阐明了脂质膜和封闭的动力蛋白丝之间的应力，对称性破坏的重要性，以及热波动的作用；这是主动收缩的结果。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.