EAGER: (ST1) Motile Matter- Reconstituting Cell Motility using Osmotic Robots

EAGER：（ST1）运动物质 - 使用渗透机器人重建细胞运动性

• 批准号: 1940020
• 负责人: Atul Parikh
• 金额: $ 30万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1940020&HistoricalAwards=false
• 关键词: EAGER; ST1; Motile; Matter; Reconstituting

Non-Technical Abstract:Biological cells are a fundamental unit of life that can harvest energy from the environment in various form, use that energy to sustain their metabolism, and direct that energy to power cellular tasks. Motility, i.e., the ability to produce controlled directional motion of a cell as a whole, is of paramount importance for the cell's ability to survive and explore its environment. Just like man-made machines use motors to enable them to move, cells use ATP-powered molecular motors to generate mechanical work. A much less explored, yet surprisingly powerful motility pathway involves propulsion-powered by osmotic energy, in which a cell directs water channels to defined regions of its membrane, and uses the resulting water fluxes in presence of external, even uniform, osmotic gradient to propel itself like a mini-rocket through aqueous environment. This project will explore the fundamental physical principles of this process by recapitulating the key elements of this motility apparatus in a model synthetic system comprised from large enclosed proto-cellular membrane compartments- giant unilamellar vesicles- and efficient synthetic water channels- carbon nanotube porins. Precisely controlled phase segregation in the vesicle shell will drive the water channels to a particular vesicle region and generate asymmetric propulsion. This project will explore the possibility of generating sustained propulsion by using multiple recharge cycles, as well as explore the effects of crowding and emergent collective behavior in the ensembles of these osmotically-propelled proto-cells. In addition, this project will provide research, training and educational opportunities to high school and undergraduate students for a better understanding of modern biomaterials research. In particular, the project will offer opportunities in biomimetic materials research through targeted outreach efforts and presentations to K-12 STEM summer program participants in California Central Valley region. It will also enable participation by undergraduate researchers through the Vertically Integrated Program (https://vip.ucdavis.edu), which allows them to work in single labs for several quarters.Technical Abstract: Cell migration is ubiquitous in biology. During motility, cells acquire a spatial asymmetry - a polarized morphology characterized by a clear distinction between the cell front and the rear - allowing them to convert energy-dissipative intracellular forces, generated in response to environmental stimuli, into net movement. In addition to ATP-consuming cytoskeleton remodeling to drive polarity and cell motility, an alternate process involves the emergence of cell polarity through active positioning of membrane channels, which in conjunction with asymmetric water fluxes under osmotic gradients generate a net propulsive force. This EAGER proposal seeks to recapitulate this essential mechanism into synthetic giant vesicles towards developing design principles for a broad general class of far-from-equilibrium materials that move, flow, or swim in response to changes in their environment. The investigators articulate a high-risk, high-reward experiments that test their central hypothesis that directional fluxes of water across vesicular compartments facilitated by asymmetric spatial distribution of highly-efficient water channels (aquaporins or carbon nanotube porins) can isothermally transduce osmotic energy into a vectorial propulsion. To address this hypothesis, three aims will be pursued: (1) Preparation and characterization of water-channel embedding vesicular compartments that exhibit cell-like polarity; (2) demonstration of self-propulsion of polarized giant vesicles in response to imposed osmotic gradients; and (3) study emergent, cooperative behaviors in populations of closely interacting, motile giant vesicles. The broader technical impact of this project benefits from a combination of concepts from the fields of soft matter, membrane biophysics, and bio-inspired materials that address fundamental interdisciplinary questions surrounding the design of model protocellular configurations, biomimicry, novel principles for material synthesis, and understanding the rules of life.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.

非技术摘要：生物细胞是一个基本的生命单位，可以以各种形式从环境中收集能量，利用该能量来维持其新陈代谢，并将能量引导到供电细胞任务。运动性，即产生整个细胞的受控方向运动的能力，对于细胞生存和探索其环境的能力至关重要。就像人造机器使用电动机使它们能够移动一样，细胞也使用ATP驱动的分子电动机来产生机械工作。渗透能量涉及的推进能量涉及的推进途径少得多，但功能强大的运动途径却涉及渗透通道的推进，并在其中将水通道引导到其膜的定义区域，并在存在外部，均匀，渗透梯度的情况下使用所得的水通量像通过水样的微型环一样推动，以推动自己的渗透梯度。 该项目将通过在模型合成系统中概括该运动设备的关键要素来探讨该过程的基本原理，该模型由大型封闭的原始细胞膜舱组成 - 巨大的UniLAMAL囊泡和有效的合成水通道 - 碳纳米管 - 碳纳米管孔。囊泡壳中精确控制的相位分离将使水通道驱动到特定的囊泡区域并产生不对称的推进。该项目将探索通过使用多个补给周期来产生持续推进的可能性，并探索在这些渗透性促进的原始细胞的集合中拥挤和新兴集体行为的影响。此外，该项目将为高中和本科生提供研究，培训和教育机会，以更好地了解现代生物材料研究。 特别是，该项目将通过针对加利福尼亚中央山谷地区的K-12 STEM夏季计划参与者的有针对性的外展工作和演讲为仿生材料研究提供机会。 它还将通过垂直整合的计划（https://vip.ucdavis.edu）来实现本科研究人员的参与，这使他们可以在单个实验室工作多个季度。技术摘要：细胞迁移在生物学上无处不在。在运动性过程中，细胞获得空间不对称性 - 一种极化形态，其特征在于细胞前和后部之间的明显区别 - 使它们能够将响应于环境刺激的响应的净运动转化为净运动。除了消耗ATP的细胞骨架重塑以驱动极性和细胞运动性外，替代过程还涉及通过膜通道的主动定位来出现细胞极性，该膜通道与渗透梯度下的不对称水磁通结合产生了净推进力。这项渴望的建议旨在将这种基本机制概括为合成的巨囊泡，以制定设计原理，以为一类远一类平衡材料一类，这些材料从环境变化中移动，流动或游泳。研究人员阐明了一个高风险，高等的实验，该实验检验了他们的中心假设，即通过高效水通道（Aquaporins或Aqubon Nanotube Porins）的不对称空间分布促进的囊泡室跨囊室的方向通量可以在等渗的渗透渗透性能量中，以使其渗透到载体上。为了解决这一假设，将追求三个目标：（1）嵌入水渠嵌入囊泡隔室的制备和表征； （2）响应施加的渗透梯度的偏振巨囊泡的自我塑造； （3）在紧密相互作用的运动巨囊泡的种群中进行研究，合作行为。该项目的更广泛的技术影响受益于软物质，膜生物物理学领域的概念和生物启发的材料的结合，这些材料涉及围绕原本构造设计的设计，生物模仿，生物模仿，新颖的材料合成原理的设计，并通过nsf的规则进行评估的规则，并理解nsf的规则，并了解了nsf的规则。智力优点和更广泛的影响审查标准。