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Force localization modes in dynamic epithelial colonies

机译:在动态上皮菌落中的力定位模式

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Collective cell behaviors, including tissue remodeling, morphogenesis, and cancer metastasis, rely on dynamics among cells, their neighbors, and the extracellular matrix. The lack of quantitative models precludes understanding of how cell–cell and cell–matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modeling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an active adherent vertex model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues.
机译:包括组织重塑,形态发生和癌症转移在内的集体细胞行为依赖于细胞,其邻居和细胞外基质之间的动力学。缺乏定量模型使人们无法了解细胞之间以及细胞与基质之间的相互作用如何调节组织尺度的力传递,从而指导形态发生过程。我们将对模型上皮组织和计算模型的生物物理测量进行整合,以探索细胞水平动力学如何在多细胞尺度上改变机械应力组织。我们表明,上皮菌落中的牵引应力分布对于相同的几何形状可以有很大的不同。对于具有牵引应力的周边定位的菌落,我们用连续模型概括了先前描述的粘性组织的机械行为。相比之下,菌落内高度运动的细胞产生的牵引应力会随时间和空间波动。为了预测牵引力动力学,我们为上皮单层细胞引入了主动粘附顶点模型(AAVM)。 AAVM预测,与我们的实验数据一致,增加的细胞运动性和减少的细胞间机械耦合将牵引力定位在菌落内部。此外,该模型捕获了由单个细胞活动(包括细胞分裂,旋转和极化迁移)引起的广泛的局部应力产生模式。这种方法提供了一个强大的定量框架,以研究细胞尺度动力学如何影响上皮组织中的力传递。

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