Computational 4D-OCM for label-free imaging of collective cell invasion and force-mediated deformations in collagen.
Computational 4D-OCM for label-free imaging of collective cell invasion and force-mediated deformations in collagen.
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DOI：
10.1038/s41598-021-81470-7
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发表时间：
2021-02-02
影响因子：
4.6
通讯作者：
Adie SG
中科院分区：
文献类型：
--
作者：
Mulligan JA;Ling L;Leartprapun N;Fischbach C;Adie SG
牵引力显微镜（TFM）是用于测量和研究与许多生物过程相关的细胞牵引力（CTF）作用的重要技术家族。然而，目前的标准TFM方法依赖于成像技术，不提供必要的实验能力，研究CTFs内的3D集体和动态系统嵌入在光学散射介质。牵引力光学相干显微镜（TF-OCM）的开发，以满足这些需求，但只被证明是用于研究孤立的细胞嵌入在光学透明的介质。在这里，我们提出了计算4D-OCM的方法，使大肿瘤球状体包埋在胶原蛋白的动态侵袭行为的研究。我们的多天，延时成像数据提供了详细的可视化不断变化的球体形态，胶原蛋白降解和胶原蛋白变形，所有使用无标记散射对比。这些能力为基质细胞如何影响癌症进展提供了见解，显着扩大了对细胞与其环境的生物物理相互作用的关键数据的访问，并为未来使用TF-OCM对集体CTF进行体积，延时重建的努力奠定了基础。
Traction force microscopy (TFM) is an important family of techniques used to measure and study the role of cellular traction forces (CTFs) associated with many biological processes. However, current standard TFM methods rely on imaging techniques that do not provide the experimental capabilities necessary to study CTFs within 3D collective and dynamic systems embedded within optically scattering media. Traction force optical coherence microscopy (TF-OCM) was developed to address these needs, but has only been demonstrated for the study of isolated cells embedded within optically clear media. Here, we present computational 4D-OCM methods that enable the study of dynamic invasion behavior of large tumor spheroids embedded in collagen. Our multi-day, time-lapse imaging data provided detailed visualizations of evolving spheroid morphology, collagen degradation, and collagen deformation, all using label-free scattering contrast. These capabilities, which provided insights into how stromal cells affect cancer progression, significantly expand access to critical data about biophysical interactions of cells with their environment, and lay the foundation for future efforts toward volumetric, time-lapse reconstructions of collective CTFs with TF-OCM.
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