Sustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy-consuming ion pumps, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, we show that mechanical loading leads to the emergence of osmotic pressure gradients between cells with consequent increases in cellular ion concentrations driving swelling. We identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model may provide new insight into the role of gap junctions in breast cancer progression.

持续增殖是癌症进展的重要驱动因素。细胞周期进展与细胞大小相关，但目前尚不清楚多个细胞如何相互作用以控制其在 3D 簇中的体积。在这项研究中，我们提出了一种机械渗透模型来研究多细胞系统内体积动力学的演化。容量控制取决于多个细胞成分之间的相互作用，包括间隙连接、机械敏感离子通道、耗能离子泵和肌动球蛋白皮层，它们协调控制细胞渗透压。在连接的细胞中，我们发现机械负荷导致细胞之间出现渗透压梯度，从而导致细胞离子浓度增加，从而导致肿胀。我们确定了间隙连接如何放大多细胞球体内细胞体积的空间变化，并进一步描述了该过程如何依赖于增殖诱导的固体应力。我们的模型可能为间隙连接在乳腺癌进展中的作用提供新的见解。