AI 中文总结
本研究通过三维智能体模型结合GMM与平均场理论，探究正常及癌细胞组织在剪切下的力学响应，揭示刚度与活性异质性决定其非仿射运动的规律，与实验结果吻合。
AI 中文摘要
生物组织的力学性质由被动力与主动力驱动，在从发育到癌症转移的多个过程中发挥关键作用。然而，组织中细胞受剪切等力学变形时的动力学响应及相关流变性质尚未得到充分表征。本研究采用三维智能体模型，针对正常组织与癌症组织，探究其在简单剪切下的响应与细胞刚度及随机主动力的函数关系。在主动力强度均匀的正常上皮组织中，屈服应力随剪切速率的变化在一定细胞体积分数范围内符合Herschel-Bulkley形式；值得注意的是，经适当标度后，剪切速率依赖性与屈服应力随弹性的变化均落在主曲线上。为模拟类癌行为，选取特定比例（$N_p$）的细胞使其具有增强的活性与降低的刚度；随着$N_p$增加，细胞集体运动程度降低，从仿射（集体）运动转变为非仿射（个体）运动，该发现与成像实验结果一致。对嵌入正常组织的刚性实体肿瘤模型（半径$R_s$）的模拟显示，随着$R_s$增大，屈服应力升高，且细胞会以集体方式迁移。高斯混合模型（GMM）与平均场理论可定量解释模拟结果及正常细胞、癌细胞、混合细胞的实验结果。该理论与实验结合的研究表明，刚度与活性的异质性决定了正常组织与癌症组织中的非仿射运动。
英文摘要
Mechanical properties of biological tissues, driven by passive and active forces, play a vital role in several processes ranging from development to cancer metastasis. However, the dynamical responses of cells in tissues, subject to mechanical deformations such as shear and the associated rheological properties, are not well characterized. Here, we use three-dimensional agent-based models for normal and cancer tissues to investigate their responses to simple shear as a function of cell stiffness and stochastic active forces. In the normal epithelium, with uniform strength of active force, the yield stress as a function of shear rate follows the Herschel-Bulkley form over a range of cell volume fraction. Strikingly, the shear rate dependence and the elasticity-dependent changes in the yield stress fall on master curves upon suitable scaling. To model cancer-like behavior, a certain fraction ($N_p$) of cells was chosen to have enhanced activity and decreased stiffness. As $N_p$ increases, the extent of collective cell movement decreases, transitioning from affine (collective) to non-affine (individualistic) movement, a finding that is in accord with imaging experiments. Simulations of a model of a stiff solid tumor, with radius $R_s$ embedded in normal tissue, show that as $R_s$ increases, the yield stress increases. Interestingly, the cells migrate collectively as $R_s$ increases. A Gaussian Mixture Model (GMM) and a mean field theory quantitatively account for the simulation as well as experimental results on cancerous, non-cancerous, and a mixture of these two types. The combined theoretical and experimental study establishes that heterogeneity in stiffness and activity determines non-affine movements in normal and cancer tissues.
