(607b) Directional Cell Migration Decision Making in 3D Confinement

Authors: 
Zhao, R., Johns Hopkins University
Afthinos, A., Johns Hopkins University
Konstantopoulos, K., Johns Hopkins University
Steering migration in cancer metastasis in response to a chemotactic stimulus has been extensively studied, yet it remains unclear how cells collect and process external cues in order to make a decision at an intersection. In a confined microenvironment, cells move preferentially to the channel of lower hydraulic resistance. In this work, by combining the microfluidic photolithography and time-lapse fluorescence microscopy, we study the decision making process of breast cancer cells at a trifurcated intersection with different hydraulic resistance on each branch. We have identified two distinct processes by which cells sense the hydraulic resistance and react to the local microenvironment. Specifically, we demonstrate that mechanosensitive ion channels mediate the sensing process and also regulate actomyosin contractility at the cell cortex, which is ultimately responsible for the decision making. Furthermore, we developed a mathematical framework integrating the aspiration model and the energy barrier theory in shape transformation to calculate and predict the percentage of cell entries in each of the three branch channels. Taken together, our work contributes to a better understanding of migratory behaviors of cancer cells under hydraulic resistance, and the mechanism of cellular signaling in response to the external environmental cues.