Modeling cell migration regulated by cell extracellular-matrix micromechanical coupling
Modeling cell migration regulated by cell extracellular-matrix micromechanical coupling
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模拟细胞外基质微机械耦合调节的细胞迁移
DOI：
10.1103/physreve.100.043303
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发表时间：
2019
影响因子：
2.4
通讯作者：
Jiao Yang
中科院分区：
文献类型：
--
作者：
Zheng Yu;Nan Hanging;Liu Yanping;Fan Qihui;Wang Xiaochen;Liu Ruchuan;Liu Liyu;Ye Fangfu;Sun Bo;Jiao Yang
纤维细胞外基质（ECM）中的细胞迁移对于许多生理和病理过程如组织再生、免疫应答和癌症进展至关重要。在迁移过程中，单个细胞可以通过肌动球蛋白收缩产生主动拉力，其通过粘着斑复合物传递到ECM纤维，重塑ECM，并最终传播到系统中的其他细胞并可以被系统中的其他细胞感知。ECM的微观结构和物理性质也会显着影响细胞迁移，例如，通过硬脊膜扩张和接触引导。在这里，我们开发了一个计算模型的二维细胞迁移调节细胞ECM微机械耦合。我们的模型明确考虑了各种细胞水平的过程，包括粘着斑的形成和拆卸，主动牵引力的产生和细胞运动，由于肌动蛋白丝收缩，在ECM中的张力的传输和传播，以及由此产生的ECM重塑。我们通过准确地再现MCF-10A乳腺癌细胞在胶原凝胶上迁移的单细胞动力学来验证我们的模型，并表明模型中考虑的细胞-ECM微机械相互作用的结果自然产生了durotaxis和接触引导效应。此外，我们的模型预测了强烈相关的多细胞迁移动力学，这是由于ECM介导的迁移细胞之间的机械耦合，并随后在使用MCF-10A细胞的体外实验中得到验证。我们的计算模型提供了一个强大的工具来研究多细胞系统在复杂的活体微环境中的涌现集体动力学，并可用于设计体外微环境，以指导集体行为和自组织的细胞。
Cell migration in fibrous extracellular matrix (ECM) is crucial to many physiological and pathological processes such as tissue regeneration, immune response, and cancer progression. During migration, individual cells can generate active pulling forces via actomyosin contraction, which are transmitted to the ECM fibers through focal adhesion complexes, remodel the ECM, and eventually propagate to and can be sensed by other cells in the system. The microstructure and physical properties of the ECM can also significantly influence cell migration, e.g., via durotaxis and contact guidance. Here, we develop a computational model for two-dimensional cell migration regulated by cell-ECM micromechanical coupling. Our model explicitly takes into account a variety of cellular-level processes, including focal adhesion formation and disassembly, active traction force generation and cell locomotion due to actin filament contraction, transmission and propagation of tensile forces in the ECM, as well as the resulting ECM remodeling. We validate our model by accurately reproducing single-cell dynamics of MCF-10A breast cancer cells migrating on collagen gels and show that the durotaxis and contact guidance effects naturally arise as a consequence of the cell-ECM micromechanical interactions considered in the model. Moreover, our model predicts strongly correlated multicellular migration dynamics, which are resulted from the ECM-mediated mechanical coupling among the migrating cell and are subsequently verified inin vitroexperiments using MCF-10A cells. Our computational model provides a robust tool to investigate emergent collective dynamics of multicellular systems in complexin vivomicroenvironment and can be utilized to designin vitromicroenvironments to guide collective behaviors and self-organization of cells.