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

卡内基梅隆大学的马库斯·萨迪诺在化学系化学理论、模型和计算方法计划的支持下，开发了极小尺度下的脂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这一奖项做出了贡献。脂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，通常将细胞分成更小的专门隔间，称为“细胞器”。在细胞分裂过程中，膜呈现出各种错综复杂的形状。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。萨迪诺教授和他的研究小组正在开发更好的理论，以了解脂膜的形状以及这如何影响细胞功能。此外，该项目通过为本科生和研究生课程(统计热力学、生物物理)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编写具有教学指导意义的脚本，来促进学习。这一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，特别努力吸引少数族裔学生学习科学。展示材料是由纸和塑料箔等日常材料制成的。能够定量地操纵这种材料的能力引导学生从直观熟悉的机械稳定性的想法，如应用于建筑物和桥梁，到他们在细胞生物学中的意外应用-与理解人体有关。该奖项支持理论和计算研究和教育，以改进在纳米尺度的脂膜弹性的定量描述。该项目寻求将膜曲率和脂质倾斜度之间的经典耦合扩展到双二次数量级，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在生物学上普遍存在的膜的情况，膜不仅由脂类混合物组成，而且两个膜叶(不对称膜)的组成可能不同。最后，该团队预测了新出现的膜特性，如边缘张力或裂变势垒，或者更一般的情况，涉及将现有弹性膜理论推向极限的高度弯曲区域。作为一种特别重要的应用，膜裂变过程正在通过理论和粗粒度计算模型相结合的方法来研究。这项工作正在阐明类脂膜和封闭的动力蛋白细丝之间的应力，对称性破坏末端效应的重要性，以及热波动的作用；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，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.