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

这项由这笔赠款支持的研究将产生关于人类上皮组织如何发挥功能和承受损害的新知识。上皮组织是覆盖在器官内外表面的细胞的薄层保护层。在整个身体中，上皮表面的主要功能之一是润滑。然而，我们对上皮润滑的大部分理解来自于对上皮表面流体的研究，而忽略了细胞本身的机械行为。该奖项支持基础研究，以建立上皮润滑和单层细胞的机械行为之间的联系。众所周知，药物干预可以改变细胞和组织的机械性能。这些将被用来揭示上皮细胞润滑的潜在机械作用。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造福于人类健康和社会。这项研究汇集了多个学科，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对研究的参与，并扩大工程教育。这项研究旨在发现单层润滑的新原理，以中心假设为指导，即与单层中细胞运动和细胞间流体运输相关的力学时间尺度产生多个不同的润滑模式。这项工作的基本原理是，在细胞集体运动和力学的基础上，重建目前对上皮润滑的理解，将出现对上皮组织功能和病理学的新观点。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，确定细胞运动和单层属性如何控制压痕动力学，并开发与集体细胞运动和单层材料和传输属性相关的润滑曲线。类似于经典的润滑现象，如流体“挤压膜”、孔弹性、边界润滑、混合润滑和流体动力润滑，将与集体细胞运动、力学和细胞间流体运输联系在一起。这一奖项反映了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。

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.