Collaborative Research: In Vitro Epithelial Lubrication: Collective Motion, Mechanics, and Fluid Transport

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The research supported by this grant will generate new knowledge about how human epithelial tissues function and endure damage. Epithelial tissues are the thin protective layers of cells that cover the inner and outer surfaces of organs. Throughout the body, one of the main functions of epithelial surfaces is lubrication. However, most of our understanding of epithelial lubrication comes from the study of fluids at epithelial surfaces, neglecting the mechanical behaviors of the cells themselves. This award supports fundamental research to establish the connection between epithelial lubrication and the mechanical behaviors of cells in monolayers. Pharmaceutical interventions are known to alter the mechanical properties of cells and tissues. These will be used to uncover the underlying mechanical contributions to epithelial lubrication. This new knowledge will increase understanding of diseases of the epithelium and identify new potential therapies. Therefore, results from this research will ultimately benefit human health and society. This research brings together several disciplines including tribology (the study of friction and wear), cell mechanics, active matter physics, and physiology. The convergence of multiple disciplines and the potential societal impacts of this work will aid in broadening participation of traditionally underrepresented groups in research and expand engineering education. The research aims to discover new principles of monolayer lubrication, guided by the central hypothesis that the mechanically relevant timescales associated with cell motion and intercellular fluid transport in monolayers generate multiple distinct regimes of lubrication. The rationale for this work is that new perspectives on epithelial tissue function and pathologies will emerge from rebuilding current understanding of epithelial lubrication on a foundation derived from collective cell motion and mechanics. The research team will classify and quantify collective motion in different types of monolayer, establish how cell motion and monolayer properties control indentation dynamics, and develop lubrication curves with connections to collective cell motion and monolayer material and transport properties. Living analogs to classic lubrication phenomena like fluid "squeeze films," poroelasticity, boundary lubrication, mixed lubrication, and hydrodynamic lubrication will be linked to collective cell motion, mechanics, and intercellular fluid transport.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.