Visualization of Apical-Basal Stress Polarity Regulating Directed Cell Migration with a FRET-Based Biosensor

Intracellular morphological apical-basal polarity, regulated by conserved polarity proteins, plays a crucial role in cell migration and metastasis. In this study, using a genetically encoded Förster resonance energy transfer (FRET) biosensor to visually present the spatiotemporal stress state between the lipid rafts on the membrane and the linked actin, we first provide the evidence for the existence of intrinsic apical-basal stress polarity in tumor cells and demonstrate that this polarity is a prerequisite for the formation of flow-induced front-back stress polarity. Interestingly, our study revealed that the front-back stress polarity disappeared upon the disruption of intrinsic apical-basal stress discrepancy, resulting in a large attenuated cell migration activity reduced from 76.2 ± 3.5% to 10 ± 4.9%. This unexpected discovery not only highlights the significance of apical-basal stress polarity as another factor influencing cell migration but also indicates that the disruption of apical-basal polarity in stress might be a novel therapeutic approach for tumor metastasis.