Lamin A/C and Vimentin as a Coordinated Regulator during Amoeboid Migration in Microscale Confined Microenvironments

Cell migration occurs in confined microenvironments,which playsa vital role in the process of tumor metastasis. However, it is challengingto study their behaviors in vivo. Here we developed a cell squeezesystem that can be scaled down to micrometers to mimic native physicalconfined microenvironments, wherein degrees of surface adhesion andmechanical constraints could be manipulated in order to investigatecell-migrating behaviors. Based on the microscale cell squeeze system,we found the synergistic role of lamin A/C and vimentin in cell transitionand migration under strong confinement. The dynamic variations inlamin A/C and vimentin expression establish a positive feedback loopin response to confinement, effectively promoting amoeboid migrationby modulating nuclear deformability while ensuring cell viability.This work shed light on modulating cell response to microenvironmentsby altering the expression of lamin A/C and/or vimentin, which maybe a more efficient way of inhibiting cancer metastasis.