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

这项资助的研究将产生关于人类上皮组织如何发挥功能和忍受损伤的新知识。上皮组织是覆盖器官内外表面的薄薄的细胞保护层。在整个身体中，上皮表面的主要功能之一是润滑。然而，我们对上皮润滑的理解大多来自于对上皮表面流体的研究，而忽略了细胞本身的力学行为。该奖项支持建立上皮润滑和单层细胞力学行为之间联系的基础研究。已知药物干预可以改变细胞和组织的机械特性。这些将用于揭示上皮润滑的潜在机械贡献。这一新知识将增加对上皮疾病的了解，并确定新的潜在治疗方法。因此，这项研究的结果最终将有益于人类健康和社会。这项研究汇集了几个学科，包括摩擦学（研究摩擦和磨损）、细胞力学、活性物质物理学和生理学。多学科的融合和这项工作的潜在社会影响将有助于扩大传统上代表性不足的群体参与研究和扩大工程教育。该研究旨在发现单层润滑的新原理，其核心假设是与单层中细胞运动和细胞间流体运输相关的机械相关时间尺度产生多种不同的润滑机制。这项工作的基本原理是，在集体细胞运动和力学的基础上，重建当前对上皮组织润滑的理解，将产生关于上皮组织功能和病理的新观点。研究小组将对不同类型的单层中的集体运动进行分类和量化，建立细胞运动和单层性质如何控制压痕动力学，并建立与集体细胞运动和单层材料和运输性质联系的润滑曲线。经典润滑现象，如流体“挤压膜”、孔隙弹性、边界润滑、混合润滑和流体动力润滑的活体类似物，将与集体细胞运动、力学和细胞间流体运输联系起来。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。

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.