Macrophages are professional phagocytes of the immune system. One of their key roles is to ingest and digest large particles, a process called phagocytosis, which involves dynamic actin reorganisation and the generation of mechanical forces. The molecular mechanisms involved in phagocytic cup formation and closure, as well as the forces involved in actomyosin contractility, are still poorly documented and understood.

 

We have recently reported the involvement of podosome-like structures in phagocytosis, which we have previously described as producing protrusion forces on the extracellular environment. In order to study the mechanics of phagocytosis, we have developed a new model of frustrated 2.5D phagocytosis consisting of flexible micropillar arrays of controlled stiffness. Using fluorescence microscopy, we are studying the dynamics of the phagocytic cup forming along the surface of the osponized pillars and have started to quantify the subcellular forces, and this approach will help to better decipher the molecular mechanisms involved in the mechanobiology of phagocytosis.

 

The project proposed to the PhD student will consist of using this innovative approach to study the molecular mechanisms involved in the generation of forces at the phagosome. This project is part of an interdisciplinary research programme that combines state-of-the-art and innovative techniques in optical and electronic imaging, cell mechanics and materials science.

 

Bibliographical references :

Jasnin M et al. Nature Communications (2022); Portes M et al. eLife (2022); van den Dries K et al. J. Cell Science (2019); Gui P et al. Cancer Immunol. Res (2018); Cervero P. et al. Nature Communication (2018); Desvignes E. et al. Nano Letters (2018); Bouissou A. et al. ACS Nano (2017); Proag A. et al. ACS Nano (2015); Labernadie A. et al. Nature Communications (2014)