Bi Dapeng, Yang Xingbo, Marchetti M Cristina, Manning M Lisa
Department of Physics, Syracuse University, Syracuse, NY, USA.
Syracuse Biomaterials Institute, Syracuse, NY, USA.
Phys Rev X. 2016 Apr-Jun;6(2). doi: 10.1103/PhysRevX.6.021011. Epub 2016 Apr 21.
Cell motion inside dense tissues governs many biological processes, including embryonic development and cancer metastasis, and recent experiments suggest that these tissues exhibit collective glassy behavior. To make quantitative predictions about glass transitions in tissues, we study a self-propelled Voronoi (SPV) model that simultaneously captures polarized cell motility and multi-body cell-cell interactions in a confluent tissue, where there are no gaps between cells. We demonstrate that the model exhibits a jamming transition from a solid-like state to a fluid-like state that is controlled by three parameters: the single-cell motile speed, the persistence time of single-cell tracks, and a target shape index that characterizes the competition between cell-cell adhesion and cortical tension. In contrast to traditional particulate glasses, we are able to identify an experimentally accessible structural order parameter that specifies the entire jamming surface as a function of model parameters. We demonstrate that a continuum Soft Glassy Rheology model precisely captures this transition in the limit of small persistence times, and explain how it fails in the limit of large persistence times. These results provide a framework for understanding the collective solid-to-liquid transitions that have been observed in embryonic development and cancer progression, which may be associated with Epithelial-to-Mesenchymal transition in these tissues.
致密组织内的细胞运动控制着许多生物学过程,包括胚胎发育和癌症转移,最近的实验表明这些组织表现出集体玻璃态行为。为了对组织中的玻璃化转变进行定量预测,我们研究了一种自推进Voronoi(SPV)模型,该模型同时捕捉汇合组织中极化的细胞运动性和多体细胞间相互作用,在这种组织中细胞之间没有间隙。我们证明该模型表现出从类似固体状态到类似流体状态的堵塞转变,这由三个参数控制:单细胞运动速度、单细胞轨迹的持续时间以及一个目标形状指数,该指数表征细胞间粘附和皮层张力之间的竞争。与传统的颗粒玻璃不同,我们能够识别一个实验上可获取的结构序参量,该参量将整个堵塞表面指定为模型参数的函数。我们证明,在小持续时间极限下,连续软玻璃流变学模型精确地捕捉了这种转变,并解释了它在大持续时间极限下失效的原因。这些结果为理解在胚胎发育和癌症进展中观察到的集体固 - 液转变提供了一个框架,这些转变可能与这些组织中的上皮 - 间充质转变有关。