Endocytosis, Cytoskeleton, and Cell Migration

Objectives and Challenges

Guillaume Montagnac’s team studies the mechanisms by which cells regulate their interactions with their environment through adhesion, mechanics, and membrane trafficking. The challenge is to understand how cells coordinate endocytosis and adhesion to adapt to physical constraints—a key process in cell migration and diseases such as cancer. The team thus aims to advance our understanding of the coupling between the plasma membrane, the cytoskeleton, and mechanical forces.

Research Areas / Major Projects

The research focuses on (i) the regulation of cell adhesions (particularly integrins and focal adhesions) by endocytic trafficking, (ii) the study of cellular responses to mechanical stresses, and (iii) the analysis of new mechanisms of membrane-environment interaction. A central focus is the study of situations where endocytosis is mechanically impeded, leading to an accumulation of specific membrane structures. This work relies on quantitative approaches combining advanced imaging, cell biology, and control of the substrate’s physical properties.

Major Findings, Future Directions, and Impacts

The team proposed and demonstrated the concept of frustrated endocytosis, in which mechanical forces exerted by the substrate or the cell prevent the internalization of vesicles, transforming endocytic structures into mechanosensitive platforms. This discovery has revealed a direct link between endocytosis, adhesion, and force perception. The research has thus shown that these structures regulate the organization of cell-cell adhesions and the adaptation of cells to their environment. Future research aims to explore these mechanisms under physiological and pathological conditions, particularly in cancer. These findings have a major impact on fundamental cell biology and open up new avenues for targeting mechanocellular interactions.