Alobaidi Amani A, Xu Yaopengxiao, Chen Shaohua, Jiao Yang, Sun Bo
Department of Physics, Oregon State University, Corvallis, OR, United States of America. These authors contributed equally to this work.
Phys Biol. 2017 Jun 28;14(4):045005. doi: 10.1088/1478-3975/aa776e.
Collective cellular dynamics in the three-dimensional extracellular matrix (ECM) plays a crucial role in many physiological processes such as cancer invasion. Both chemical and mechanical signaling support cell-cell communications on a variety of length scales, leading to collective migratory behaviors. Here we conduct experiments using 3D in vitro tumor models and develop a phenomenological model in order to probe the cooperativity of force generation in the collective invasion of breast cancer cells. In our model, cell-cell communication is characterized by a single parameter that quantifies the correlation length of cellular migration cycles. We devise a stochastic reconstruction method to generate realizations of cell colonies with specific contraction phase correlation functions and correlation length a. We find that as a increases, the characteristic size of regions containing cells with similar contraction phases grows. For small a values, the large fluctuations in individual cell contraction phases smooth out the temporal fluctuations in the time-dependent deformation field in the ECM. For large a values, the periodicity of an individual cell contraction cycle is clearly manifested in the temporal variation of the overall deformation field in the ECM. Through quantitative comparisons of the simulated and experimentally measured deformation fields, we find that the correlation length for collective force generation in the breast cancer diskoid in geometrically micropatterned ECM (DIGME) system is [Formula: see text], which is roughly twice the linear size of a single cell. One possible mechanism for this intermediate cell correlation length is the fiber-mediated stress propagation in the 3D ECM network in the DIGME system.
三维细胞外基质（ECM）中的集体细胞动力学在许多生理过程（如癌症侵袭）中起着关键作用。化学信号和机械信号都支持细胞间在各种长度尺度上的通讯，从而导致集体迁移行为。在此，我们使用三维体外肿瘤模型进行实验，并开发了一个唯象模型，以探究乳腺癌细胞集体侵袭过程中力产生的协同性。在我们的模型中，细胞间通讯由一个单一参数表征，该参数量化了细胞迁移周期的相关长度。我们设计了一种随机重建方法，以生成具有特定收缩相位相关函数和相关长度α的细胞集落实现。我们发现，随着α的增加，包含具有相似收缩相位细胞的区域的特征尺寸会增大。对于较小的α值，单个细胞收缩相位的大波动会平滑细胞外基质中随时间变化的变形场的时间波动。对于较大的α值，单个细胞收缩周期的周期性会在细胞外基质中整体变形场的时间变化中清晰显现。通过对模拟和实验测量的变形场进行定量比较，我们发现，在几何微图案化细胞外基质（DIGME）系统中的乳腺癌盘状结构中，集体力产生的相关长度为[公式：见原文]，大约是单个细胞线性尺寸的两倍。这种中等细胞相关长度的一种可能机制是DIGME系统中三维细胞外基质网络中纤维介导的应力传播。
