CAREER: Cellular Mechanics at the Nanoscale: Lipid Membrane Elasticity and Force Transduction in Mechanosensitive Proteins

佛蒙特大学和州立农业学院的Juan M. Vanegas由化学系化学理论、模型和计算方法（CTMC）项目和刺激竞争研究（EPSCoR）项目共同资助，通过新颖的计算方法在纳米尺度上表征细胞成分对物理刺激的机械行为和反应。Vanegas教授开发了最先进的计算工具来研究纳米尺度生物力学领域的两个基本问题。第一个问题是“脂肪（脂质）结构在模型生物膜中的作用是什么？”第二个问题是，“蛋白质如何感知外部物理刺激，比如压力？”回答这些问题对于理解生物系统在膜裂变和融合、细胞器和细胞形成、心血管控制和发育、渗透调节、触摸和疼痛感知等过程中的功能是至关重要的。Vanegas教授的团队开发的开源计算工具和方法使生物化学、生物物理学和材料科学等其他领域的广泛研究成为可能。该CAREER提案的教育部分侧重于将佛蒙特大学的物理入门课程转变为积极的学习工作室/工作坊环境，旨在显著提高对核心概念的理解，并增加女性和代表性不足的少数民族的参与。瓦内加斯教授还积极参与招生和开发新课程，以支持佛蒙特大学新成立的物理学博士项目。生物膜和机械敏感通道的力学是通过开发和应用最先进的分子模拟工具在分子动力学和局部应力/弹性计算中的研究。Juan M. Vanegas教授的这一职业建议围绕两个独立但高度互补的研究目标展开，旨在了解生物分子（如脂质和膜蛋白）的分子结构与机械偶联的生物功能之间的联系。研究部分侧重于两个主要任务。这些包括从分子动力学模拟中直接估计局部和宏观弹性模量，以及通过非平衡模拟在机械敏感蛋白中进行力传导和门控的能量学。Vanegas教授正在开发创新的计算方法，通过计算微观应力和弹性张量（测量材料内部的局部力平衡和弹性响应），从分子模型中捕获机械性能。这些类连续场提供了分子结构、纳米级力学性能和大尺度力学行为之间的独特联系。Vanegas开发的互补导向模拟方法进一步允许在机械敏感通道中有效地探索机械驱动的生物过程，以建立其功能的总体框架。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。

Juan M. Vanegas of The University of Vermont & State Agricultural College is jointly funded by the the Chemical Theory, Models and Computational Methods (CTMC) program in the Division of Chemistry and the Established Program to Stimulate Competitive Research (EPSCoR) to characterize the mechanical behavior and response of cellular components to physical stimuli at the nanometer scale through novel computational methods. Professor Vanegas develops state of the art computational tools to investigate two fundamental questions in the area of nano-scale biomechanics. The first question is "What is the role of fat (lipid) structure in a model biomembrane?" The second question is, "How does a protein sense external physical stimuli such as pressure?" Answering these questions is essential to understanding how biological systems function during membrane fission and fusion, organelle and cellular shaping, cardiovascular control and development, osmotic regulation, and touch and pain sensing. The open-source computational tools and methods developed by Professor Vanegas’ group are enabling a broad range of studies on other areas of biochemistry, biophysics, and materials science. The educational component of this CAREER proposal focuses on transitioning introductory physics courses at the University of Vermont to an active learning studio/workshop environment designed to significantly improve understanding of core concepts and increasing participation from women and underrepresented minorities. Professor Vanegas is also actively participating in student recruitment and developing new curriculum to support the newly-established Ph.D. program in physics at the University of Vermont. Mechanics of biomembranes and mechanosensitive channels are investigated through the development and application of state of the art molecular simulation tools in steered molecular dynamics and local stress/elasticity calculations. This CAREER proposal by Professor Juan M. Vanegas pivots around two independent yet highly complementary research objectives aimed at understanding the connection between the molecular structure of biomolecules such as lipids and membrane proteins and mechanically-coupled, biological functions. The research component focuses on two main tasks. These include the direct estimation of local and macroscopic elastic moduli from molecular dynamics simulations, and force transduction and energetics of gating in mechanosensitive proteins through non-equilibrium simulations. Professor Vanegas is developing innovative computational methods to capture mechanical properties from molecular models through calculation of the microscopic stress and elasticity tensors which measure the local balance of forces and elastic response within a material. These continuum-like fields provide a unique connection between molecular structure, mechanical properties at the nanoscale, and large scale mechanical behaviors. Complimentary steered simulation methods developed by Vanegas further allow efficient exploration of mechanically-driven biological processes in mechanosensitive channels to establish a general framework for their function.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.