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

非技术摘要：生物细胞是生命的基本单位，可以从环境中以各种形式收集能量，利用这些能量维持他们的新陈代谢，并将这些能量引导到细胞任务中。运动性，即细胞作为一个整体产生受控定向运动的能力，对于细胞的生存和探索环境的能力是至关重要的。就像人造机器使用马达来使它们移动一样，细胞使用三磷酸腺苷驱动的分子马达来产生机械功。另一种研究较少，但却令人惊讶的强大运动途径涉及推进--由渗透能量驱动，细胞将水通道引导到其膜的特定区域，并在外部甚至均匀的渗透梯度存在的情况下利用由此产生的水通量来推动自己，就像小型火箭在水环境中一样。这个项目将通过在一个模型合成系统中概括这一运动装置的关键元素来探索这一过程的基本物理原理，该模型合成系统由大型封闭的原始细胞膜隔室-巨大的单层囊泡-和有效的合成水通道-碳纳米管孔道组成。囊泡外壳中精确控制的相分离将驱动水通道到特定的囊泡区域，并产生不对称的推进。这个项目将探索通过使用多个补充周期来产生持续推进的可能性，以及在这些渗透推进的原始细胞群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向加州中央山谷地区的K-12 STEM夏季项目参与者介绍，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://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，细胞获得了空间不对称性--一种两极分化的形态，其特征是细胞的前部和后部有明显的区别--允许它们将响应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之外，另一种过程涉及通过主动定位膜通道来出现细胞极性，这与渗透梯度下不对称的水通量一起产生净推动力。这项急切的提案试图将这一基本机制概括为合成巨大的囊泡，以制定一类广泛的远离平衡的材料的设计原则，这些材料可以随着环境的变化而移动、流动或游泳。研究人员阐述了一项高风险、高回报的实验，以检验他们的中心假设，即高效水通道(水通道或碳纳米管孔蛋白)的不对称空间分布促进了水在泡囊间的定向流动，可以等温地将渗透能量转化为矢量推进。为了解决这一假说，将追求三个目标：(1)制备和表征嵌入呈现细胞样极性的水通道的囊泡；(2)展示极化的巨泡响应于施加的渗透梯度而自推进；以及(3)研究密切相互作用的、可移动的巨泡种群中的紧急、合作行为。该项目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的结合，这些概念解决了围绕模型原细胞构型设计、生物仿生学、材料合成的新原理以及对生命规则的理解的基本跨学科问题。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.