The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization
The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization
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DOI：
10.1007/s10237-014-0581-9
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发表时间：
2015-01-01
影响因子：
3.5
通讯作者：
Duda, Georg N.
中科院分区：
文献类型：
--
作者：
Checa, Sara;Rausch, Manuel K.;Duda, Georg N.
物理线索在广泛的生物过程中发挥着重要作用，如胚胎发生、伤口愈合、肿瘤侵袭和结缔组织形态发生。虽然众所周知，在这些过程中，细胞通过细胞牵引力不断与局部细胞外基质（ECM）相互作用，但这些机械相互作用在大规模细胞和基质组织中的作用在很大程度上仍然未知。在这项研究中，我们使用一个简单的理论模型来研究细胞和基质组织作为细胞和周围ECM之间的机械反馈信号的结果。该模型包括通过细胞牵引力使ECM变形和通过基质变形触发细胞迁移的双向耦合。此外，我们结合了基质纤维的机械贡献和细胞的重组。我们表明，即使在均匀的环境中，一组收缩细胞也会大规模地自极化。此外，我们的模拟模拟了实验观察到的细胞在最大刚度方向上的排列以及作为细胞和纤维重组的结果的张力的建立。此外，我们证明细胞组织与细胞和基质之间的机械反馈回路紧密相连。对硬环境有偏好的细胞倾向于形成链，而对软环境有偏好的细胞倾向于形成簇。这里提出的模型说明了简单物理线索的潜力及其对细胞自组织的影响。它可以用于细胞-基质相互作用发挥关键作用的应用，例如在组织工程支架的设计中，以及在器官发生或组织再生中获得模式形成的基本理解。
Physical cues play a fundamental role in a wide range of biological processes, such as embryogenesis, wound healing, tumour invasion and connective tissue morphogenesis. Although it is well known that during these processes, cells continuously interact with the local extracellular matrix (ECM) through cell traction forces, the role of these mechanical interactions on large scale cellular and matrix organization remains largely unknown. In this study, we use a simple theoretical model to investigate cellular and matrix organization as a result of mechanical feedback signals between cells and the surrounding ECM. The model includes bi-directional coupling through cellular traction forces to deform the ECM and through matrix deformation to trigger cellular migration. In addition, we incorporate the mechanical contribution of matrix fibres and their reorganization by the cells. We show that a group of contractile cells will self-polarize at a large scale, even in homogeneous environments. In addition, our simulations mimic the experimentally observed alignment of cells in the direction of maximum stiffness and the building up of tension as a consequence of cell and fibre reorganization. Moreover, we demonstrate that cellular organization is tightly linked to the mechanical feedback loop between cells and matrix. Cells with a preference for stiff environments have a tendency to form chains, while cells with a tendency for soft environments tend to form clusters. The model presented here illustrates the potential of simple physical cues and their impact on cellular self-organization. It can be used in applications where cell-matrix interactions play a key role, such as in the design of tissue engineering scaffolds and to gain a basic understanding of pattern formation in organogenesis or tissue regeneration.