Department of Engineering, Cambridge University, Cambridge CB2 1PZ, UK.
Department of Engineering, Cambridge University, Cambridge CB2 1PZ, UK.
Biophys J. 2022 Nov 15;121(22):4394-4404. doi: 10.1016/j.bpj.2022.08.030. Epub 2022 Aug 24.
Cell-cell interaction dictates cell morphology and organization, which play a crucial role in the micro-architecture of tissues that guides their biological and mechanical functioning. Here, we investigate the effect of cell density on the responses of cells seeded on flat substrates using a novel statistical thermodynamics framework. The framework recognizes the existence of nonthermal fluctuations in cellular response and thereby naturally captures entropic interactions between cells in monolayers. In line with observations, the model predicts that cell area and elongation decrease with increasing cell seeding density-both are a direct outcome of the fluctuating nature of the cellular response that gives rise to enhanced cell-cell interactions with increasing cell crowding. The modeling framework also predicts the increase in cell alignment with increasing cell density: this cellular ordering is also due to enhanced entropic interactions and is akin to nematic ordering in liquid crystals. Our simulations provide physical insights that suggest that entropic cell-cell interactions play a crucial role in governing the responses of cell monolayers.
细胞间相互作用决定了细胞的形态和组织,这在指导组织生物和机械功能的微观结构中起着至关重要的作用。在这里,我们使用一种新的统计热力学框架研究了细胞密度对接种在平基底上的细胞反应的影响。该框架认识到细胞反应中存在非热波动,从而自然地捕捉到单层细胞间的熵相互作用。与观察结果一致,该模型预测细胞面积和伸长率随细胞接种密度的增加而减小——这都是细胞反应的波动性质的直接结果,这种波动性质导致细胞拥挤程度增加时细胞间相互作用增强。建模框架还预测了随着细胞密度的增加细胞排列的增加:这种细胞有序性也是由于增强的熵相互作用,类似于液晶中的向列有序性。我们的模拟提供了物理见解,表明熵细胞-细胞相互作用在调节细胞单层的反应中起着至关重要的作用。