Microchannel Stiffness and Confinement Jointly Induce the Mesenchymal-Amoeboid Transition of Cancer Cell Migration

The physical confinement of cell microenvironment could enhance the invasive capability and drug resistance of cancer cells. However, due to the lack of in vitro experimental platform to mimic both stiffness and confinement of the tumor microenvironment, the underlying mechanism remains elusive. Here, we developed a hydrogel-based microchannel platform with independently tunable channel stiffness and width in a physiological range. We found that the migration speed of the cancer cell is influenced by the synergistic effect of channel stiffness and width. In addition, the mesenchymal-amoeboid transition has a strong correlation with the channel stiffness. Besides, with a developed computational model, the role of nuclear stiffness on cancer migration speed and thus the mesenchymal-amoeboid transition in microchannels was also revealed. This platform is capable of mimicking the native physical microenvironment during metastasis, providing a powerful tool for high-throughput screening applications and investigating the interaction between cancer migration and biophysical microenvironment.