Supracellular Measurement of Spatially Varying Mechanical Heterogeneities in Live Monolayers.
Supracellular Measurement of Spatially Varying Mechanical Heterogeneities in Live Monolayers.
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DOI：
10.1016/j.bpj.2022.08.024
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发表时间：
2022-08
影响因子：
3.4
通讯作者：
Alexandra Bermudez;Zachary Gonzalez;Bao Zhao;Ethan Salter;Xuanqing Liu;Leixin Ma;M. Jawed;Cho-Jui Hsieh;Neil Y. C. Lin
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文献类型：
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作者：
Alexandra Bermudez;Zachary Gonzalez;Bao Zhao;Ethan Salter;Xuanqing Liu;Leixin Ma;M. Jawed;Cho-Jui Hsieh;Neil Y. C. Lin
组织的机械性能对广泛的生物过程有深远的影响，如胚胎发育（1，2），伤口愈合（3-6）和疾病进展（7）。具体而言，细胞的空间变化模量在很大程度上影响局部组织变形和细胞间的相互作用。尽管表征这种异质机械性质的重要性，但仍然难以以高通量和最小扰动测量活细胞层中的超细胞模量场。在这项工作中，我们开发了一个单层有效模量测量集成自定义细胞担架，光学显微镜，和基于AI的推理。我们的方法首先量化了轻微拉伸的细胞层的非均匀变形，并使用AI推理将测量的应变场转换为有效的模量场。这种方法使我们能够直接可视化数千个单元的有效模量分布。我们的特征在于上皮细胞和成纤维细胞的有效细胞模量的平均值，SD和相关长度，这与以前的结果一致。我们还观察到细胞面积和硬度之间的轻度相关性堵塞上皮细胞，表明细胞模量的影响，包装。总的来说，我们报道的实验平台提供了一种有价值的替代细胞力学测量工具，可以与基于显微镜的表征相结合。
The mechanical properties of tissues have profound impacts on a wide range of biological processes such as embryo development (1,2), wound healing (3–6), and disease progression (7). Specifically, the spatially varying moduli of cells largely influence the local tissue deformation and intercellular interaction. Despite the importance of characterizing such a heterogeneous mechanical property, it has remained difficult to measure the supracellular modulus field in live cell layers with a high-throughput and minimal perturbation. In this work, we developed a monolayer effective modulus measurement by integrating a custom cell stretcher, light microscopy, and AI-based inference. Our approach first quantifies the heterogeneous deformation of a slightly stretched cell layer and converts the measured strain fields into an effective modulus field using an AI inference. This method allowed us to directly visualize the effective modulus distribution of thousands of cells virtually instantly. We characterized the mean value, SD, and correlation length of the effective cell modulus for epithelial cells and fibroblasts, which are in agreement with previous results. We also observed a mild correlation between cell area and stiffness in jammed epithelia, suggesting the influence of cell modulus on packing. Overall, our reported experimental platform provides a valuable alternative cell mechanics measurement tool that can be integrated with microscopy-based characterizations.