Cell swelling, softening and invasion in a three-dimensional breast cancer model

Yu Long Han, Adrian F. Pegoraro, Hui Li, Kaifu Li, Yuan Yuan, Guoqiang Xu, Zichen Gu, Jiawei Sun, Yukun Hao, Satish Kumar Gupta, Yiwei Li, Wenhui Tang, Hua Kang, Lianghong Teng, Jeffrey J. Fredberg & Ming Guo

Control of the structure and function of three-dimensional multicellular tissues depends critically on the spatial and temporal coordination of cellular physical properties, yet the organizational principles that govern these events and their disruption in disease remain poorly understood. Using a multicellular mammary cancer organoid model, we map here the spatial and temporal evolution of positions, motions and physical characteristics of individual cells in three dimensions. Compared with cells in the organoid core, cells at the organoid periphery and the invasive front are found to be systematically softer, larger and more dynamic. These mechanical changes are shown to arise from supracellular fluid flow through gap junctions, the suppression of which delays the transition to an invasive phenotype. These findings highlight the role of spatiotemporal coordination of cellular physical properties in tissue organization and disease progression.

DOI