Aerospace Engineering and Mechanics, University of Minnesota, Minneapolis, MN, USA.
Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI, USA.
J R Soc Interface. 2021 Feb;18(175):20200823. doi: 10.1098/rsif.2020.0823. Epub 2021 Feb 17.
Through mechanical forces, biological cells remodel the surrounding collagen network, generating striking deformation patterns. Tethers-tracts of high densification and fibre alignment-form between cells, thinner bands emanate from cell clusters. While tethers facilitate cell migration and communication, how they form is unclear. Combining modelling, simulation and experiment, we show that tether formation is a densification phase transition of the extracellular matrix, caused by buckling instability of network fibres under cell-induced compression, featuring unexpected similarities with martensitic microstructures. Multiscale averaging yields a two-phase, bistable continuum energy landscape for fibrous collagen, with a densified/aligned second phase. Simulations predict strain discontinuities between the undensified and densified phase, which localizes within tethers as experimentally observed. In our experiments, active particles induce similar localized patterns as cells. This shows how cells exploit an instability to mechanically remodel the extracellular matrix simply by contracting, thereby facilitating mechanosensing, invasion and metastasis.
通过机械力,生物细胞重塑周围的胶原网络,产生引人注目的变形模式。细胞之间形成了连接物——高致密性和纤维排列的束——细胞簇发出较细的带状物。虽然连接物有助于细胞迁移和通讯,但它们是如何形成的尚不清楚。通过结合建模、模拟和实验,我们表明,连接物的形成是细胞诱导压缩下的网络纤维的屈曲不稳定性引起的细胞外基质的致密化相转变,其具有与马氏体微观结构出乎意料的相似性。多尺度平均产生了纤维胶原的两相、双稳态连续体能量景观,具有致密化/排列的第二相。模拟预测了未致密化和致密化相之间的应变不连续性,这在实验中被观察到在连接物内局部化。在我们的实验中,活性粒子诱导出与细胞类似的局部模式。这表明细胞如何通过收缩利用不稳定性来机械重塑细胞外基质,从而促进机械感知、入侵和转移。