Events Calendar

Roxanne Glazier (MGH): Imaging integrin receptor mechanics in invasive structures
Tuesday 29 September 2020, 12:00pm - 01:00pm
Mechanical forces play a critical role in cell biology and disease. The primary mediators of molecular mechanotransduction are integrin receptors, which sense and respond to the mechanical microenvironment by applying picoNewton (pN, 1012 N) forces to ligands in the extracellular matrix and on adjacent cells. These forces guide cell fate and function. An emerging class of integrin-based adhesion is the podosome. Podosomes are actin-rich structures, which facilitate cell invasion and migration, as well as bone resorption. Podosome-like structures in cancer cells are typically called invadopodia and promote metastasis. Podosomes consist of a striking 3D architecture in which an adhesion ring surrounds a dense and dynamically polymerizing actin core. It was previously shown that podosomes are mechanosensitive and exert pushing forces on their substrate using actin polymerization. However, understanding the fundamental mechanism of podosome mechanoregulation has remained challenging due to a lack of suitable and sensitive tools. In this work we combine DNA nanotechnology, biomaterials, and advanced fluorescence to map and manipulate integrin receptor forces in podosomes. We demonstrate that podosomes apply pN integrin tension to sense molecular substrate stiffness. We show that integrin tension and actin polymerization act in a direct feedback and that tensile forces enhance podosome formation and maturation. In addition, this work contributes new tools for the broad study of receptor-ligand interactions.


Location : Goitein Room