Mechanical Cell-Cell Communication in Fibrous Networks: The Importance of Network Geometry.
Mechanical Cell-Cell Communication in Fibrous Networks: The Importance of Network Geometry.
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DOI：
10.1007/s11538-016-0242-5
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发表时间：
2017-03
影响因子：
3.5
通讯作者：
Gaffney EA
中科院分区：
文献类型：
--
作者：
Humphries DL;Grogan JA;Gaffney EA
在细胞外基质（ECM）中收缩的细胞可以长距离传递压力，将它们的位置和方向传达给数十微米外的细胞。当细胞接种在具有线性弹性性质的基底上时，如聚丙烯酰胺（PA）凝胶，没有观察到这种现象。纤维基质支持深远的应力和应变场的能力对许多生理过程有影响，而ECM的机械特性对几个病理过程（包括肿瘤侵袭和纤维化）至关重要。理论模型已经研究了ECM在各种网络几何结构中的性质。然而，网络架构对机械细胞间通讯的影响却很少受到关注。这项工作研究了几何形状对网络力学的影响，从而研究了细胞通过不同网络进行机械通信的能力。细胞衍生的位移场量化为各种网络的几何形状，同时控制网络拓扑结构，交联密度和微观力学性能。我们发现，响应的异质性，纤维对齐，和基板位移场是敏感的网络选择。此外，我们表明，某些几何形状支持机械通信比其他更长的距离。因此，我们预测，网络几何形状的选择是重要的纤维基质中的细胞-细胞相互作用的基本建模，以及在实验环境中，在细胞尺度上的机械信号起着重要的作用。因此，这项工作为基底力学的理论模型的构建和机械细胞间通讯的实验探索提供了信息。
Cells contracting in extracellular matrix (ECM) can transmit stress over long distances, communicating their position and orientation to cells many tens of micrometres away. Such phenomena are not observed when cells are seeded on substrates with linear elastic properties, such as polyacrylamide (PA) gel. The ability for fibrous substrates to support far reaching stress and strain fields has implications for many physiological processes, while the mechanical properties of ECM are central to several pathological processes, including tumour invasion and fibrosis. Theoretical models have investigated the properties of ECM in a variety of network geometries. However, the effects of network architecture on mechanical cell–cell communication have received little attention. This work investigates the effects of geometry on network mechanics, and thus the ability for cells to communicate mechanically through different networks. Cell-derived displacement fields are quantified for various network geometries while controlling for network topology, cross-link density and micromechanical properties. We find that the heterogeneity of response, fibre alignment, and substrate displacement fields are sensitive to network choice. Further, we show that certain geometries support mechanical communication over longer distances than others. As such, we predict that the choice of network geometry is important in fundamental modelling of cell–cell interactions in fibrous substrates, as well as in experimental settings, where mechanical signalling at the cellular scale plays an important role. This work thus informs the construction of theoretical models for substrate mechanics and experimental explorations of mechanical cell–cell communication.