Multiscale Mechanics of Cell Interactions With Flexible Nanofilaments

细胞与柔性纳米丝相互作用的多尺度力学

• 批准号: 1562904
• 负责人: Huajian Gao
• 金额: $ 45.91万
• 依托单位: Brown University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1562904&HistoricalAwards=false
• 关键词: Multiscale; Mechanics; Cell; Interactions; Flexible

Flexible nanofilaments are fundamental components of man-made materials, living cells and of viruses such as Ebola. The importance to human health of nanofilaments is highlighted by the recent outbreak of Ebola virus disease in West Africa, which began in 2013 and continued for over two years. Understanding how nanofilaments enter living cells, therefore, has important relevance to society. This project is aimed to understand how flexible nanofilaments interact and enter human and animal cells, thereby helping address the urgent societal needs to understand the life cycle of filoviruses as well as the potential health hazards of engineered nanomaterials. Results from this research will benefit the U.S. economy and society, as engineered nanomaterials are becoming a significant fraction of material flows in the U.S. and most of the manufactured nanomaterials will eventually end up in landfills, hence impacting our ecosystem and health. The multi-disciplinary approach of the research will positively impact engineering education and outreach activities at Brown University. The educational programs will provide training for graduate students and visiting scholars, as well as research experience for undergraduate students. This work will address the following fundamental mechanics issues that underlie a vast variety of experimental observations in the field: (1) attachment of flexible nanofilaments onto a cell membrane, (2) fusion of membranes that envelop nanofilaments, (3) biopackaging of flexible nanofilaments, and (4) budding of nanofilaments from a cell membrane. The technical approaches will be based on a number of theoretical and simulation techniques developed by the PIs research group in cell mechanics. This work will provide useful insights into the kinetics of cell processing of nanofilaments through theoretical modeling and large scale coarse-grained molecular dynamics simulations of protein-mediated nucleation of adhesion domains with considerations of receptor diffusion, binding kinetics and membrane undulation, membrane fusion focusing on the effects of size, shape and bending rigidity of enveloped nanofilaments and compositions of lipid membranes, determination of phase diagrams of cell packaging of nanofilaments and filament networks with respect to the length, elastic properties and interaction between nanofilaments and cell membranes, and effects of mechanical properties and cell interactions on modes of nanofilament budding. The ultra-large scale simulations in the work will be performed at the National Institute for Computational Sciences, and the rest of the computational work will be performed at the Center for Computing and Visualization at Brown University.

柔性纳米丝是人造材料，活细胞和埃博拉病毒的基本组成部分。 最近在2013年始于2013年的埃博拉病毒疾病爆发，持续了两年多的埃博拉病毒疾病，强调了纳米丝健康的重要性。 因此，了解纳米丝如何进入活细胞与社会具有重要意义。该项目的目的是了解柔性纳米丝如何相互作用并进入人类和动物细胞，从而有助于满足紧急社会的需求，以了解丝状病毒的生命周期以及工程纳米材料的潜在健康危害。这项研究的结果将使美国的经济和社会受益，因为工程纳米材料正在成为美国的大部分物质流动，大多数制造的纳米材料最终最终将最终出现在垃圾填埋场中，从而影响我们的生态系统和健康。该研究的多学科方法将对布朗大学的工程教育和外展活动产生积极影响。这些教育计划将为研究生和访问学者提供培训，并为本科生提供研究经验。 这项工作将解决以下基本的机制问题，这些问题是该领域中各种各样的实验观察的基础：（1）柔性纳米丝的附着在细胞膜上，（2）包裹纳米丝的膜的融合，（3）（3）柔性纳米燃料的生物包装，（3）柔性纳米燃料的buthofiments，以及（4）unanofilarane of a inanofding of a imbrane a inanofding osbrane y yananofding量量。技术方法将基于PIS研究小组在细胞力学中开发的许多理论和仿真技术。这项工作将通过理论建模和大规模的粗粒细胞分子动力学模拟蛋白质介导的粘附域介导的成核，考虑受体扩散，结合动力学和膜融合的大小和逐渐构成的繁殖，对粘附域的成核的构成，将粘附域介导的蛋白质介导的成核对蛋白质介导的成核的构成，从而提供有用的见解。脂质膜，确定纳米丝和细丝网络相对于纳米丝和细胞膜之间的长度，弹性性能以及相互作用的细胞包装相图，以及机械性能和细胞相互作用在纳米芽芽模式上的影响。工作中的超大标度模拟将在美国国家计算科学研究所进行，其余的计算工作将在布朗大学的计算与可视化中心进行。