Three-dimensional cancer cell migration directed by dual mechanochemical guidance
Three-dimensional cancer cell migration directed by dual mechanochemical guidance
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DOI：
10.1103/physrevresearch.4.l022007
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发表时间：
2022-04-12
影响因子：
4.2
通讯作者：
Sun, Bo
中科院分区：
文献类型：
--
作者：
Esfahani, Pedram;Levine, Herbert;Sun, Bo
由外部信号引导的定向细胞迁移在许多生理和病理生理过程中发挥着核心作用。细胞的微环境通常同时包含各种线索，而细胞对多重引导的运动反应知之甚少。在这里，我们结合实验和数学模型来研究乳腺癌细胞在接触引导和趋化梯度存在下的三维迁移。我们发现，由于细胞外基质（ECM）的微观结构在空间上发生变化，接触引导的存在使细胞的趋化性变得复杂。在存在双重引导的情况下，ECM 对准的影响在外部由 ECM 纤维的一致性决定，在内部由细胞机械传感 Rho/Rock 通路决定。当接触引导与化学梯度平行时，连贯的 ECM 纤维显着提高趋化效率。当接触引导垂直于化学梯度时，细胞利用 ECM 紊乱来定位趋化路径。我们的结果强调了充分表征癌细胞微环境的重要性，以便更好地了解侵袭和转移。
Directed cell migration guided by external cues plays a central role in many physiological and pathophysiological processes. The microenvironment of cells often simultaneously contains various cues and the motility response of cells to multiplexed guidance is poorly understood. Here we combine experiments and mathematical models to study the three-dimensional migration of breast cancer cells in the presence of both contact guidance and a chemoattractant gradient. We find that the chemotaxis of cells is complicated by the presence of contact guidance as the microstructure of extracellular matrix (ECM) vary spatially. In the presence of dual guidance, the impact of ECM alignment is determined externally by the coherence of ECM fibers and internally by cell mechanosensing Rho/Rock pathways. When contact guidance is parallel to the chemical gradient, coherent ECM fibers significantly increase the efficiency of chemotaxis. When contact guidance is perpendicular to the chemical gradient, cells exploit the ECM disorder to locate paths for chemotaxis. Our results underscore the importance of fully characterizing the cancer cell microenvironment in order to better understand invasion and metastasis.