Molecular Simulations of Biological Active Matter

生物活性物质的分子模拟

• 批准号: 1800418
• 负责人: Garegin Papoian
• 金额: $ 45万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800418&HistoricalAwards=false
• 关键词: Molecular; Simulations; Biological; Active; Matter

Garegin Papoian of the University of Maryland College Park is supported by an award from the Chemical Theory, Models, and Computational Methods Program in the Division of Chemistry to develop, optimize, and apply the MEDYAN (MEchanical DYnamics of Active Networks) computational framework for modeling chemomechanical active matter. The Condensed Matter and Materials Theory Program in the Division of Materials Research also contributes to this award. Traditional states of matter, such as solids, liquids, and gases, self-organize through interactions among constituent molecules. Active matter, on the other hand, arises from external energy-driven self-assembly. Such systems are challenging to model due to the strong intrinsic coupling of chemistry and mechanics. Active matter has emerged as a new frontier in science, at the interface of chemistry, materials physics, and biology. In fact, the cells in one's body can be viewed as a form of highly complex active matter, where the external energy is derived from food. Within each cell, an elaborate interplay of interacting molecular motors, self-assembling filaments, the cell membrane, and organelles continuously convert chemical energy into forces that determine cellular shape, motility, and sensing of the extracellular environment. Papoian's group, by developing and applying the MEDYAN software framework, is working toward the grand challenge of modeling individual cells in all of their extraordinary complexity, by incorporating new models of the cell's constituent chemical, mechanical, and transport processes. MEDYAN is thus enabling critical new understanding of the molecular principles underlying cellular active matter. As part of this project, MEDYAN is being used to study self-assembly and structural stability of dendritic spines in neurons, which support formation of long-term memories in the brain, and cell shape oscillations, whose origin and biological role are not well understood. The software has applications to biomaterials as well as to cell biology and is expected to advance the national health. MEDYAN is being made available to the public as open source software, and an active matter community website and learning resource is being developed as part of the project. Research is coupled with education and outreach through inclusion of high school students in lab research, and ongoing efforts to expand diversity in applicants within the university's chemical physics program.This project is extending MEDYAN to support essential components of eukaryotic cell modeling. These include a deformable, chemically-active plasma membrane model expressed in terms of a 2D mesh and associated Voronoi polygons; incorporation of a free energy penalty for in-plane and out-of-plane membrane deformations; steric and tethering interactions of cytoskeletal filaments with local membrane patches; volumetric forces due to osmotic pressure or associated with the volume conservation; and reaction-diffusion of membrane bound proteins, including the ability of some proteins to induce spontaneous membrane curvature. These advances are further leveraged to formulate computational models for internal organelles such as the cell nucleus. In addition, a model is being constructed to describe self-assembly of spectrin proteins into a dynamically rearranging 2D sheet transiently tethered underneath the plasma membrane. To achieve the computational efficiency needed for simulating at biologically-relevant length- and timescales, MEDYAN is being parallelized on state-of-the-art CPU and GPU architectures. These new modeling and simulation capabilities are being used to study two important problems in cell biology: the molecular underpinnings of the structural stability of dendritic spines, which underlie the stability of long-term memories in animals; and collective oscillatory cycles, propagating as a migrating front from one cell to another, which are based on a cytoskeletal phenomenon called pulsatility. For both of these projects, there is close collaboration with an experimentalist on iterative model development and validation. This next generation of MEDYAN is providing important new modeling capabilities with applications to programmable matter integrating active and non-active components to achieve smart materials with unique properties. The MEDYAN software and documentation are freely disseminated as open source. As part of this project, Dr. Papoian is creating a community web resource centered around active matter, with class-ready educational materials for secondary schools, undergraduate and graduate courses, and research sections bringing together information on publications relating to active matter and the scientific groups working in the field.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.

马里兰大学帕克分校的Garegin Papoian得到了化学系化学理论、模型和计算方法计划的支持，以开发、优化和应用Medyan(主动网络机械动力学)计算框架来模拟化学机械活性物质。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。物质的传统状态，如固体、液体和气体，通过组成分子之间的相互作用而自组织。另一方面，活性物质来自外部能量驱动的自组装。由于化学和力学的强烈内在耦合，这类系统的建模具有挑战性。活性物质在化学、材料物理和生物学的交界处已经成为一个新的科学前沿。事实上，一个人体内的细胞可以被视为一种高度复杂的活性物质，其中外部能量来自食物。在每个细胞内，相互作用的分子马达、自组装的细丝、细胞膜和细胞器的复杂相互作用不断地将化学能转化为决定细胞形状、运动和对细胞外环境的感知的力。Papoian的团队通过开发和应用Medyan软件框架，正在通过整合细胞组成的化学、机械和运输过程的新模型，致力于在所有非凡的复杂性中对单个细胞进行建模的重大挑战。因此，Medyan使人们能够对细胞活性物质背后的分子原理有批判性的新理解。作为该项目的一部分，Medyan正在被用于研究神经元中树突棘的自组装和结构稳定性，树突棘支持大脑中长期记忆的形成，以及细胞形状振荡，其起源和生物学作用尚不清楚。该软件在生物材料和细胞生物学方面都有应用，预计将促进国民健康。Medyan正在作为开放源码软件向公众提供，作为该项目的一部分，正在开发一个活动物质社区网站和学习资源。研究与教育和推广相结合，通过将高中生纳入实验室研究，以及不断努力扩大大学化学物理项目申请者的多样性。该项目正在扩展Medyan，以支持真核细胞建模的基本组成部分。这些包括用二维网格和相关的Voronoi多边形表示的可变形的、具有化学活性的质膜模型；引入了平面内和面外膜变形的自由能惩罚；细胞骨架细丝与局部膜补丁的空间相互作用和系链相互作用；渗透压引起的体积力或与体积守恒有关的体积力；以及膜结合蛋白的反应扩散，包括一些蛋白质诱导自发膜弯曲的能力。这些进展被进一步用来制定内部细胞器的计算模型，如细胞核。此外，正在构建一个模型来描述幽灵蛋白自组装成一个动态重新排列的2D片层，该片层在质膜下短暂地捆绑在一起。为了在生物相关的长度和时间尺度上实现模拟所需的计算效率，Medyan正在最先进的CPU和GPU架构上并行化。这些新的建模和模拟能力正被用于研究细胞生物学中的两个重要问题：树突棘结构稳定性的分子基础，它是动物长期记忆稳定性的基础；集体振荡周期，作为从一个细胞到另一个细胞的迁移前沿传播，基于一种称为脉动性的细胞骨架现象。对于这两个项目，都与实验者在迭代模型开发和验证方面进行了密切合作。这一新一代Medyan正在提供重要的新建模能力，将有源和非有源组件集成到可编程物质中，以实现具有独特性能的智能材料。Medyan软件和文档作为开放源码免费分发。作为该项目的一部分，Papoian博士正在创建一个以活动物质为中心的社区网络资源，为中学、本科和研究生课程以及研究部分收集与活动物质相关的出版物和该领域工作的科学团体的信息。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。

项目成果

Membrane-MEDYAN: Simulating Deformable Vesicles Containing Complex Cytoskeletal Networks

Membrane-MEDYAN：模拟包含复杂细胞骨架网络的可变形囊泡

• DOI: 10.1021/acs.jpcb.1c02336
• 发表时间: 2021
• 期刊: The Journal of Physical Chemistry B
• 作者: Ni, Haoran;Papoian, Garegin A.
• 通讯作者: Papoian, Garegin A.

Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling

• DOI: 10.1371/journal.pcbi.1007156
• 发表时间: 2019-07-01
• 期刊: PLOS COMPUTATIONAL BIOLOGY
• 影响因子: 4.3
• 作者: Chandrasekaran, Aravind;Upadhyaya, Arpita;Papoian, Garegin A.
• 通讯作者: Papoian, Garegin A.

Segmental Lennard-Jones interactions for semi-flexible polymer networks

• DOI: 10.1080/00268976.2021.1910358
• 发表时间: 2021-04-09
• 期刊: MOLECULAR PHYSICS
• 影响因子: 1.7
• 作者: Floyd, Carlos;Chandresekaran, Aravind;Papoian, Garegin A.
• 通讯作者: Papoian, Garegin A.

Tensile force-induced cytoskeletal remodeling: Mechanics before chemistry

• DOI: 10.1371/journal.pcbi.1007693
• 发表时间: 2020-06-01
• 期刊: PLOS COMPUTATIONAL BIOLOGY
• 影响因子: 4.3
• 作者: Li, Xiaona;Ni, Qin;Jiang, Yi
• 通讯作者: Jiang, Yi

Turnover versus treadmilling in actin network assembly and remodeling

肌动蛋白网络组装和重塑中的周转与跑步

• DOI: 10.1002/cm.21564
• 发表时间: 2019
• 期刊: Cytoskeleton
• 影响因子: 2.9
• 作者: Ni, Qin;Papoian, Garegin A.
• 通讯作者: Papoian, Garegin A.