Reseach center : IPBS TEAM: "PHAGOCYTE ARCHITECTURE AND DYNAMICS" TEL: +33 5 61 17 54 72
STUDY OF ACTIN ARCHITECTURE AND CROSSLINKING IN PODOSOME FORCE GENERATION
Macrophages infiltration in body tissues is critical for immune protection, but it also helps progression of inflammatory diseases and cancers. We have shown that to migrate within the cancer stroma, macrophages use the mesenchymal migration mode that involves adhesion cell structures called podosomes. Thanks to the development of a method called Protrusion Force Microscopy, we could estimate the protrusive force generated by podosomes and show that it requires combined acto-myosin contraction and actin polymerization. Podosomes are composed of a core of F-actin surrounded by adhesion complexes. The scope of our study is to decipher the podosome architecture to determine how it generates protrusive foces. We are now questioning the organization and regulation of actin filaments in podosome cores using a combination of force measurements, optical nanoscopy and cryo-electron tomography. We aim to reveal the specific localization and function of actin crosslinkers, alpha actinin 1, filamin A, fascin and L-plastin, and how filaments are collectively organized. Progressing in the knowledge of podosomes may help to identify pharmacological targets to limit tissue infiltration of macrophages in several diseases