ABSTRACT

The membranes of living cells are highly and selectively permeable to water. Variations in the osmotic pressure due to dissolved molecules drives water transport across the membrane, thereby inducing fluid flows and membrane motions. Such flows are critical to biological processes such as the regulation of cell water content, the transport of intra- and extracellular compartments, and the migration of cells in tissues. Despite their importance, the fundamental fluid mechanics underlying these processes remains poorly understood. This project aims to advance our understanding of fluid flows and membrane motions driven by osmotic gradients. Such knowledge will further enable biotechnologies involving the extraction, separation, and delivery of extracellular vesicles, which are actively pursued as diagnostic and therapeutic tools for treating human diseases. The project will also provide educational opportunities to middle and high school students from underrepresented groups through laboratory tours and summer research experiences.

The central goal of the research is to develop experimental platforms and theoretical models that elucidate the physical mechanisms underlying the motion of lipid vesicles in osmotic gradients ? a process called osmophoresis. Using microfluidic systems, the research will quantify vesicle velocity as a function of membrane properties such as vesicle size, permeability, rigidity, tension / excess area, and surface charge as well as environmental properties such as solute type, gradient magnitude, fluid viscosity, and confinement. Notably, the project will use lipid membranes incorporating aquaporin water channels to create high permeability vesicles that mimic native exosomes. The experiments will provide definitive data with which to enhance our understanding of osmophoresis and its impact on vesicle transport in biology. The proposed theory will integrate previous work on the osmophoresis of rigid spherical membranes with models of membrane dynamics that account for deformation and flow within incompressible lipid bilayers. The theoretical investigations will ultimately reproduce and explain experimental observations of rapid vesicle motions in osmotic gradients. Finally, the demonstration of osmophoretic vesicle sorting will provide a fundamental basis for biotechnologies involving the separation and characterization of extracellular vesicles.

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.

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