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：生物细胞是生命的基本单位，可以以各种形式从环境中获取能量，利用这些能量维持新陈代谢，并将这些能量用于细胞任务。运动性，即，产生细胞作为一个整体的受控定向运动的能力对于细胞的生存和探索其环境的能力至关重要。就像人造机器使用马达来使它们移动一样，细胞使用ATP驱动的分子马达来产生机械功。一种探索较少但令人惊讶的强大运动途径涉及由渗透能提供动力的推进，其中细胞将水通道引导到其膜的限定区域，并在外部甚至均匀的渗透梯度存在下使用所得的水通量来推动自身像微型火箭一样通过水性环境。 该项目将探索这一过程的基本物理原理，方法是在一个模型合成系统中重现这种运动装置的关键要素，该模型合成系统由大型封闭的原细胞膜隔室-巨型单层囊泡-和有效的合成水通道-碳纳米管孔蛋白组成。囊泡壳中精确控制的相分离将驱动水通道到特定的囊泡区域并产生不对称推进。该项目将探索通过使用多个充电周期产生持续推进的可能性，以及探索这些自主推进的原细胞集合中的拥挤和紧急集体行为的影响。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，该项目将通过有针对性的外展工作和演示文稿，为加州中央谷地区的K-12 STEM夏季项目参与者提供仿生材料研究的机会。 它还将使本科生研究人员能够通过垂直整合计划（https：//www.example.com）参与，该计划允许他们在单个实验室工作几个季度。技术摘要：细胞迁移在生物学中无处不在。vip.ucdavis.edu在运动过程中，细胞获得了空间不对称性--一种以细胞前部和后部之间的明显区别为特征的极化形态--使它们能够将响应环境刺激而产生的能量耗散细胞内力转化为净运动。除了消耗ATP的细胞骨架重塑以驱动极性和细胞运动性之外，另一个过程涉及通过膜通道的主动定位出现细胞极性，其与渗透梯度下的不对称水通量结合产生净推进力。EAGER的提案旨在将这一基本机制概括为合成巨型囊泡，以制定广泛的一般类远离平衡的材料的设计原则，这些材料会根据环境的变化而移动，流动或游泳。研究人员阐述了一个高风险，高回报的实验，测试他们的中心假设，即通过高效水通道（水通道蛋白或碳纳米管孔蛋白）的不对称空间分布促进的水穿过囊泡隔室的定向通量可以等温地将渗透能量转化为矢量推进。为了解决这一假设，将追求三个目标：（1）水通道包埋囊泡室，表现出细胞样极性的制备和表征;（2）证明极化的巨囊泡响应于施加的渗透梯度的自推进;和（3）研究密切相互作用，能动的巨囊泡群体中的涌现，合作行为。该项目更广泛的技术影响受益于软物质，膜生物物理学和生物启发材料领域的概念组合，这些概念解决了围绕模型原细胞配置设计，仿生学，材料合成新原理，该奖项反映了NSF的法定使命，并通过使用基金会的知识产权进行评估，被认为值得支持。优点和更广泛的影响审查标准。