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.

摘要：生物细胞是生命的基本单位，它可以从环境中以各种形式获取能量，利用这些能量维持自身的新陈代谢，并指导这些能量为细胞任务提供动力。运动性，即细胞作为一个整体产生可控定向运动的能力，对于细胞生存和探索其环境的能力至关重要。就像人造机器使用马达使其运动一样，细胞使用atp驱动的分子马达来产生机械功。一个很少被探索，但却令人惊讶地强大的运动途径涉及渗透能量驱动的推进，在这个过程中，细胞将水通道引导到膜的特定区域，并在外部均匀渗透梯度存在的情况下利用所产生的水通量像微型火箭一样推动自己通过水环境。该项目将探索这一过程的基本物理原理，通过在一个模型合成系统中概述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分隔室（巨大的单层囊泡）和高效的合成水通道（碳纳米管孔）组成。在囊泡壳中精确控制相分离，将水通道驱动到特定的囊泡区域，并产生不对称推进。该项目将探索通过多次充电循环产生持续推进的可能性，以及探索这些渗透推进的原细胞集合中拥挤和紧急集体行为的影响。此外，该项目将为高中生和本科生提供研究、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讲，为加州中央山谷地区K-12 STEM暑期项目的参与者提供仿生材料研究的机会。它还将允许本科生研究人员通过垂直整合计划（https://vip.ucdavis.edu）参与其中，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普遍存在。在运动过程中，细胞获得了一种空间不对称——一种以细胞前部和后部明显区分为特征的极化形态——允许它们将因环境刺激而产生的能量耗散的细胞内力转化为净运动。除了消耗atp的细胞骨架重塑来驱动极性和细胞运动外，另一个过程包括通过主动定位膜通道来产生细胞极性，这与渗透梯度下的不对称水通量一起产生净推进力。这个EAGER提案试图将这一基本机制概括为合成巨囊泡，以开发一种广泛的非平衡材料的设计原则，这些材料可以随着环境的变化而移动、流动或游动。研究人员提出了一个高风险、高回报的实验，以验证他们的中心假设，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了水的定向通量，可以等温地将渗透能转化为矢量推进。为了解决这一假设，将追求三个目标：(1)制备和表征具有细胞样极性的水通道嵌入囊泡室；(2)极化巨泡在渗透梯度作用下的自我推进；(3)研究密切互动的运动巨囊泡群体中的紧急合作行为。该项目的更广泛的技术影响得益于软物质、膜生物物理学和生物启发材料领域的概念结合，这些概念解决了围绕模型原细胞结构设计、仿生学、材料合成新原理和理解生命规则的基本跨学科问题。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。