Direct Test of the Tensional Homeostasis Hypothesis with Force Microscopy

该奖项的研究目标是了解收缩细胞如何利用来自其物理微环境的信息来动态控制其收缩。观察到不同组织中的细胞产生不同程度的张力，这导致了“张力稳态”的概念，即细胞自身组织起来，在给定的组织内保持恒定的张力。作为该项目的一部分，开展的研究将直接在单细胞中测试这一假设，使用力显微镜与微图案化相结合来控制细胞粘连，并使用荧光显微镜来跟踪参与张力产生的关键分子。这项工作将开发新的实验技术来量化细胞对机械信号的反应，并确定涉及机械传感的分子机制。这个项目将解决机械生物学中的基本问题，这些问题有可能阐明细胞用来维持适当的生理组织功能的机械控制参数。这项工作还将通过建立本构关系来推动细胞力学计算模型的发展。与该项目相关的教育计划将为中学理科学生和普通公众提供新的机会，让他们了解力学在生物学中的作用。将开展中学生活动，向他们介绍所在环境中物体的材料特性，并将开发关于人体内材料特性的展览，以便在社区科学活动中展示。这两项活动将包括本科生和研究生，并有助于提高他们向非科学家交流科学的能力。

The research objective of this award is to understand how contractile cells use information from their physical microenvironment to dynamically control their contraction. The observation that cells in different tissues generate different amounts of tension has led to the concept of ?tensional homeostasis?, in which a cell organizes itself to maintain a constant tension within a given tissue. Studies conducted as part of this project will directly tests this hypothesis in single cells using force microscopy combined with micropatterning to control cell adhesions and fluorescence microscopy to track key molecules involved in tension generation. This work will develop new experimental techniques for quantifying the response of cells to mechanical signals and identify molecular mechanisms involved in mechanosensing. This project will address basic questions in mechanobiology that have the potential to clarify the mechanical control parameters cells use to maintain proper physiological tissue function. This work will also advance the development of computational models of cell mechanics by establishing constitutive relationships. The educational plan associated with this project will provide new opportunities for middle school science students and the general public to learn about the role of mechanics in biology. Activities for middle school students will be developed that introduce them to the material properties of objects in their environment, and an exhibit on properties of materials within the human body will be developed for presentation at community science events. Both activities will include undergraduate and graduate students and help to improve their ability to communicate science to non-scientists.