Mapping Collective Forces of Lung Cancer Spheroids Using Traction Force Microscopy

Epithelial tissues actively deform their surrounding extracellular matrix mechanically. Traction forces represent an intrinsic mechanism by which cells actively sense and adapt to their extracellular environment, which has been increasingly recognized to play a crucial role in cancer progression, metastasis, and treatment failure. However, current traction force research has predominantly concentrated at the single-cell level, overlooking the multicellular spatio-temporal dynamics and collective effects inherent in cancer as an integrated multi-cellular system. Herein, the collective-level traction forces of cancer spheroids were mapped using traction force microscopy. Our results revealed an inherent spatial distribution pattern of cancer spheroid traction force at the spheroid-substrate contact plane, with peaks concentrated along the periphery of the contact interface. Besides, the cancer spheroid traction force was regulated by the spheroid size when the spheroid did not undergo dispersion, which was positively correlated with the spheroid dispersion ability. Moreover, there existed an inherent temporal correlation between the spheroid traction force and dispersion. The onset of cancer spheroid dispersion was accompanied with a marked suppression of the traction force dynamics. Furthermore, the traction force of cancer spheroids was validated to hold potential as a biomechanics-related phenotypic readout for anticancer drug testing.