Cholesterol Flip-Flop Dynamics and Nanomechanical Response of Deformed Biomembranes: Experiments and Petascale Simulations

该奖项的研究目标是将联合收割机实验和计算机模拟相结合，以研究细胞膜组成、组织和力学行为之间的关系。细胞膜对机械应力的纳米级响应是重要的生物物理过程的一个重要方面，例如胞内和胞吐作用、病毒融合和出芽以及细胞内运输。在该奖项下进行的联合实验模拟研究将探讨分子过程，如膜脂质和胆固醇翻转跨越细胞膜双层的相分离成液体有序和液体无序结构域，如何调节膜的纳米机械响应。新开发的计算工具包括一个千万亿次计算框架，用于执行嵌入粗粒度MD模拟的数百万个原子MD模拟。这些研究将显著增加对细胞膜弯曲力学的生物物理理解，这对病毒感染和神经元通信具有深远意义。教育计划的重点是一个双学位课程，其中学生完成博士学位。在他们自己的学科要求，而对硕士研究。在计算机科学中。双学位的学生将帮助组织计算科学研讨会的代表性不足的群体，这是在南加州大学定期举行。教育推广计划还将高中学生纳入实验研究。

The research objective of this award is to combine experiment and computer simulation to investigate the relationships between cell membrane composition, organization, and mechanical behavior. The nanoscale response of cell membranes to mechanical stress is an essential aspect of important biophysical processes such as endo- and exocytosis, viral fusion and budding, and intracellular trafficking. The joint experimental-simulation studies conducted under this award will probe how molecular processes such as phase separation into liquid-ordered and liquid-disordered domains by membrane lipids and cholesterol flip-flop across the cell membrane bilayer modulate the nanomechanical response of membranes. Newly developed computational tools include a petascale computational framework to perform multimillion-atom MD simulations embedded in coarse-grained MD simulations.These studies will add significantly to biophysical understanding of bending mechanics of cell membranes, which has profound implications for viral infection and neuron communication. The educational plan focuses on a dual-degree program in which students fulfill Ph.D. requirements within their own discipline while studying towards an M.S. in computer science. Dual-degree students will help organize computational science workshops for underrepresented groups, which are held regularly at the University of Southern California. The educational outreach plan also integrates high-school students into experimental research.