Department of Quantum Matter Physics, University of Geneva, 1211, Geneva, Switzerland.
G.W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Sci Rep. 2021 Apr 23;11(1):8869. doi: 10.1038/s41598-021-86684-3.
Juxtacellular interactions play an essential but still not fully understood role in both normal tissue development and tumour invasion. Using proliferating cell fronts as a model system, we explore the effects of cell-cell interactions on the geometry and dynamics of these one-dimensional biological interfaces. We observe two distinct scaling regimes of the steady state roughness of in-vitro propagating Rat1 fibroblast cell fronts, suggesting different hierarchies of interactions at sub-cell lengthscales and at a lengthscale of 2-10 cells. Pharmacological modulation significantly affects the proliferation speed of the cell fronts, and those modulators that promote cell mobility or division also lead to the most rapid evolution of cell front roughness. By comparing our experimental observations to numerical simulations of elastic cell fronts with purely short-range interactions, we demonstrate that the interactions at few-cell lengthscales play a key role. Our methodology provides a simple framework to measure and characterise the biological effects of such interactions, and could be useful in tumour phenotyping.
细胞旁相互作用在正常组织发育和肿瘤侵袭中起着至关重要但尚未完全理解的作用。我们使用增殖细胞前沿作为模型系统，探索细胞-细胞相互作用对这些一维生物界面的几何形状和动力学的影响。我们观察到体外增殖的 Rat1 成纤维细胞前沿的稳定状态粗糙度呈现出两种不同的标度律，这表明在亚细胞尺度和 2-10 个细胞尺度上存在不同层次的相互作用。药物调节显著影响细胞前沿的增殖速度，那些促进细胞迁移或分裂的调节剂也导致细胞前沿粗糙度的最快演变。通过将我们的实验观察结果与具有纯短程相互作用的弹性细胞前沿的数值模拟进行比较，我们证明了少数细胞尺度上的相互作用起着关键作用。我们的方法为测量和描述这种相互作用的生物学效应提供了一个简单的框架，并且在肿瘤表型分析中可能有用。
