Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making
Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making
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DOI：
10.1038/s41467-019-12155-z
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发表时间：
2019-09-13
影响因子：
16.6
通讯作者：
Reinhart-King, Cynthia A.
中科院分区：
文献类型：
--
作者：
Zanotelli, Matthew R.;Rahman-Zaman, Aniqua;Reinhart-King, Cynthia A.
在侵袭-转移级联过程中的细胞迁移需要癌细胞在空间复杂的微环境中导航，该微环境为迁移细胞提供方向选择。在这里，我们调查细胞能量学迁移决策过程中在有限的空间。理论和实验数据表明，通过有限的空间迁移的能量成本介导的细胞和矩阵的兼容性之间的平衡，以及直接决策的空间限制的程度。能量成本，由细胞的工作需要产生力的矩阵位移，增加细胞刚度，矩阵刚度，和空间限制的程度，限制迁移。通过评估可能的迁移路径之间的能量成本，我们可以预测迁移选择的概率。我们的研究结果表明，在密闭空间的运动性对迁移细胞提出了高能量的要求，细胞迁移的方向限制最少，以尽量减少能源成本。因此，治疗靶向代谢可以限制癌细胞迁移和转移。
Cell migration during the invasion-metastasis cascade requires cancer cells to navigate a spatially complex microenvironment that presents directional choices to migrating cells. Here, we investigate cellular energetics during migration decision-making in confined spaces. Theoretical and experimental data show that energetic costs for migration through confined spaces are mediated by a balance between cell and matrix compliance as well as the degree of spatial confinement to direct decision-making. Energetic costs, driven by the cellular work needed to generate force for matrix displacement, increase with increasing cell stiffness, matrix stiffness, and degree of spatial confinement, limiting migration. By assessing energetic costs between possible migration paths, we can predict the probability of migration choice. Our findings indicate that motility in confined spaces imposes high energetic demands on migrating cells, and cells migrate in the direction of least confinement to minimize energetic costs. Therefore, therapeutically targeting metabolism may limit cancer cell migration and metastasis.