BRIGE: Active micro-rheology with spherical micro-confinement: A model for intracellular transport

BRIGE：具有球形微约束的主动微流变学：细胞内运输模型

• 批准号: 1342218
• 负责人: Roseanna Zia
• 金额: $ 17.5万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1342218&HistoricalAwards=false
• 关键词: BRIGE; Active; micro; rheology; spherical

Technical Description:The goal of this BRIGE proposal is to build a research and education program to discover and develop predictive theory for the active and passive transport of particles inside 3D-microscopically confined and concentrated complex fluids, with a view toward a model of intracellular transport inside eukaryotic cells. The interior of a eukaryotic cell is an active, crowded aqueous compartment that is populated by a multitude of nano-scale particles. Emerging studies suggest that much cellular function--e.g. metabolism, pattern formation, and cargo transport--is affected by simple physical transport, including diffusion and active towing by motor proteins. Several important open questions must be answered to understand how such motion affects cell function: What is the origin of anomalous diffusive behavior of particles in the cytoplasm? Does gradient diffusion or cytoplasmic streaming (or both) enable particle migration during pattern formation, division, and growth? What are the effects of micro-confinement? Recent models attempting to answer these questions assume a quiescent and unbound fluid, but the cytoplasmic fluid undergoes bulk advection due to its entrainment by self-propelled motor proteins, and even 1D confinement dramatically alters transport behavior.To approach this problem, the PI will construct a 3D simulation model utilizing the framework of Stokesian Dynamics, the premier technique for accurate modeling of particle-laden fluids. Prior to utilizing the simulation, however, theoretical work is required to develop the so-called mobility tensors?hydrodynamical "rules" for the way particles interact with each other and with an enclosure?and similar functions for representing the motion of self-propelled motor proteins. Equilibrium, gradient diffusion, and imposed flows that mirror motion inside a cell will be studied. The statistical distribution of particles, diffusion coefficients, effective viscosity, and stress will be computed. The simulation results will be compared to our theory that connects stress gradients to particle migration, and to experimental results.The intellectual merit of such understanding is high: the rheological behavior of fully 3D-confined suspensions is a largely unexplored area and thus constitutes a substantive and novel contribution to the rheology field. This knowledge will advance our understanding of the effects of finite domains on the rate at which energy is dissipated in Brownian systems.Broader Significance and Importance:The knowledge developed will create greater understanding of the dynamical fluid environment and transport inside the cell, will advance our understanding of how such processes are related to disease, and will facilitate the development of therapeutic tools. It will uniquely broaden connections between cell biology, engineering, and statistical physics by creating a novel first-principles model that can be built upon by any of these fields.Broadening Participation of Underrepresented Groups in Engineering:To broaden participation in STEM fields by under-represented minority students and to reach out to the general public, we will work to improve the interest, participation, and skills of such students in science by teaching critical skills: using the scientific method; identifying physical processes to predict behavior; and connecting mathematics to physical problems. To achieve this goal, the PI will develop interactive demonstrations and disseminate them via (1) Cornell classes; (2) Cornell outreach programs; and (3)quarterly "Science Scrimmage Days" at a National Academy Foundation high school for underrepresented minority students.This research has been funded through the Broadening Participation Research Initiation Grants in Engineering solicitation, which is part of the Broadening Participation in Engineering Program of the Engineering Education and Centers Division.

技术描述：这项布里奇计划的目标是建立一个研究和教育计划，以发现和发展粒子在3D显微镜下受限和浓缩的复杂流体中的主动和被动运输的预测理论，以期建立一个真核细胞内的细胞内运输模型。真核细胞的内部是一个活跃的、拥挤的房水隔间，里面填充着大量纳米级的颗粒。新出现的研究表明，许多细胞功能--例如。新陈代谢、图案形成和货物运输--受简单的物理运输的影响，包括马达蛋白质的扩散和主动拖曳。要了解这种运动如何影响细胞功能，必须回答几个重要的开放问题：细胞质中颗粒异常扩散行为的起源是什么？在图案形成、分裂和生长过程中，梯度扩散或细胞质流动(或两者兼而有之)能使颗粒迁移吗？微禁闭的效果是什么？最近试图回答这些问题的模型假定流体是静止的和无结合的，但胞质流体由于其自身推进的马达蛋白的夹带而经历大量平流，甚至一维限制都会显著改变传输行为。为了解决这个问题，PI将利用Stokesian Dynamic框架构建一个3D模拟模型，该框架是精确模拟含颗粒流体的主要技术。然而，在利用模拟之前，需要进行理论工作来开发所谓的迁移率张量--粒子相互作用以及与封闭空间相互作用的流体动力学“规则”--以及代表自行车式马达蛋白质运动的类似函数。将学习平衡、梯度扩散和反映细胞内部运动的外加流动。将计算颗粒的统计分布、扩散系数、有效粘度和应力。模拟结果将与我们将应力梯度与颗粒迁移联系起来的理论以及实验结果进行比较。这种理解的学术价值很高：完全三维约束悬浮液的流变行为在很大程度上是一个未被探索的领域，因此构成了对流变学领域的实质性和新颖性的贡献。这些知识将促进我们对有限区域对布朗系统中能量耗散率的影响的理解。更广泛的意义和重要性：所开发的知识将使我们更好地理解细胞内的动态流体环境和运输，将促进我们对这些过程如何与疾病相关的理解，并将促进治疗工具的开发。它将独特地拓宽细胞生物学、工程学和统计物理学之间的联系，创建一个新的第一原理模型，可以在这些领域的任何一个领域建立起来。扩大未被充分代表的少数群体参与工程学：为了扩大未被充分代表的少数族裔学生对STEM领域的参与，并接触普通公众，我们将努力通过教授关键技能来提高这些学生对科学的兴趣、参与和技能：使用科学方法；识别预测行为的物理过程；以及将数学与物理问题联系起来。为了实现这一目标，国际工程学院将开发互动演示，并通过(1)康奈尔大学课堂；(2)康奈尔大学外展计划；(3)在国家科学院基金会一所高中为未被充分代表的少数族裔学生举办每季度一次的“科学混战日”。这项研究的资金来自工程教育和中心分部扩大工程参与计划的一部分--扩大工程招揽中的参与研究启动补助金。