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

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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.