Abstract Cumulative evidence shows that microenvironmental conditions play a significant role in the regulation of cell functions, and how cells respond to these conditions are of central importance to regenerative medicine and cancer cell response to therapeutics. Here, we develop a new method to examine cell mechanical properties by analyzing the motion of nanoparticles in living in mice, combining particle tracking with intravital microscopy. This method directly examines the mechanical response of breast carcinoma cells and normal breast epithelial cells under intravital microenvironments. Our results show both carcinoma and normal cells display significantly reduced compliance (less deformability) in vivo compared to the same cells cultured in 2D, in both sparse and confluent conditions. While the compliance of the normal cells remains steady over time, the compliance of carcinoma cells decreases further as they form tumor-like architectures. Integrating the cancer cells into spheroids embedded in 3D collagen matrices in part redirected the mechanical response to a state closer to the in vivo setting. Overall, our study demonstrates that the microenvironment is a crucial regulator of cell mechanics and the intravital particle tracking method can provide novel insights into the role of cell mechanics in vivo.

中文翻译：

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活体癌细胞的粒子追踪微流变学

摘要 累积证据表明，微环境条件在细胞功能的调节中起着重要作用，而细胞如何对这些条件做出反应对于再生医学和癌细胞对治疗的反应至关重要。在这里，我们开发了一种新方法，通过分析小鼠体内纳米粒子的运动，将粒子追踪与活体显微镜相结合，来检查细胞机械特性。该方法直接检查活体微环境下乳腺癌细胞和正常乳腺上皮细胞的机械反应。我们的结果显示，与在 2D 中培养的相同细胞相比，在稀疏和汇合条件下，癌细胞和正常细胞在体内的顺应性显着降低（变形性更小）。虽然正常细胞的顺应性随着时间的推移保持稳定，但癌细胞的顺应性随着它们形成肿瘤样结构而进一步降低。将癌细胞整合到嵌入 3D 胶原基质的球体中，部分地将机械反应重定向到更接近体内环境的状态。总的来说，我们的研究表明，微环境是细胞力学的关键调节器，活体粒子追踪方法可以为体内细胞力学的作用提供新的见解。