Using Histologic Image Analysis to Understand Biophysical Regulations of Epithelial Cell Morphology

Alexandra Bermudez, Samanta Negrete Muñoz, Rita Blaik, Amy C. Rowat, Jimmy Hu, Neil Y.C. Lin
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Abstract

Epithelial mechanics and mechanobiology have become 2 important research fields in life sciences and bioengineering. These fields investigate how physical factors induced by cell adhesion and collective behaviors can directly regulate biologic processes, such as organ development and disease progression. Cell mechanics and mechanobiology thus make exciting biophysics education topics to illustrate how fundamental physics principles play a role in regulating cell biology. However, the field currently lacks hands-on activities that engage students in learning science and outreach programs in these topics. One such area is the development of robust hands-on modules that allow students to observe features of cell shape and mechanics and connect them to fundamental physics principles. Here, we demonstrate a workflow that engages students in studying epithelial cell mechanics by using commercial histology slides of frog skin. We show that by using recently developed artificial intelligence–based image-segmentation tools, students can easily quantify different cell morphologic features in a high-throughput manner. Using our workflow, students can reproduce 2 essential findings in cell mechanics: the common gamma distribution of normalized cell aspect ratio in jammed epithelia and the constant ratio between the nuclear and cellular area. Importantly, because the only required instrument for this active learning module is a readily available light microscope and a computer, our module is relatively low cost, as well as portable. These features make the module scalable for students at various education levels and outreach programs. This highly accessible education module provides a fun and engaging way to introduce students to the world of epithelial tissue mechanics.
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利用组织学图像分析了解上皮细胞形态的生物物理调节机制
上皮力学和力学生物学已成为生命科学和生物工程的两个重要研究领域。这些领域研究由细胞粘附和集体行为诱导的物理因子如何直接调节生物过程,如器官发育和疾病进展。细胞力学和力学生物学因此成为令人兴奋的生物物理教育主题,说明基本物理原理如何在调节细胞生物学中发挥作用。然而,该领域目前缺乏让学生参与学习科学的实践活动和这些主题的推广计划。其中一个领域是开发强大的动手模块,使学生能够观察细胞形状和力学的特征,并将它们与基本物理原理联系起来。在这里,我们展示了一个工作流程,通过使用青蛙皮肤的商业组织学幻灯片,使学生参与研究上皮细胞力学。我们表明,通过使用最近开发的基于人工智能的图像分割工具,学生可以轻松地以高通量方式量化不同的细胞形态特征。使用我们的工作流程,学生可以重现细胞力学中的两个基本发现:堵塞上皮中归一化细胞宽高比的共同伽马分布以及核与细胞面积之间的恒定比。重要的是,由于这种主动学习模块所需的唯一仪器是一台现成的光学显微镜和一台计算机,因此我们的模块成本相对较低,并且便携。这些功能使该模块可扩展到不同教育水平和外展项目的学生。这个高度可访问的教育模块提供了一个有趣和引人入胜的方式,向学生介绍上皮组织力学的世界。
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