Physical and Molecular Principles Governing Cytoskeletal Organization
Our goal is to understand how cytoskeletal proteins cooperate for cells to exert forces or resist mechanical stress.
The cellular cytoskeleton is composed of proteins that can polymerize in the form of tubes or filaments. These biological polymers form a dense and organized meshwork that allows cells to resist mechanical constraints, or to exert forces through the action of molecular motors or from the reorganization of these networks. The cytoskeleton is essential for many cellular functions such as migration or division.
All known living organisms have a cytoskeleton, and some polymers such as actin and microtubules are extremely conserved in eukaryotes. In mammals, many diseases and in particular certain types of cancers are related to defects of the cytoskeleton. Thus, understanding from a fundamental point of view all the subtleties of its functioning is essential to explain certain pathological cellular behaviors.
The main objective of the team is therefore to understand how the polymers of the cytoskeleton and their multiple associated regulatory proteins function together in the cell. To solve this problem, we mainly adopt a reductionist approach based on the idea that any biological process is well understood from the moment when we are able to reconstitute it from its most elementary building blocks. Our work therefore consists first of identifying key molecules through genetic and cell biology approaches. Then, the purification and biochemical analysis of these compounds allows us to predict their functions within complex molecular interaction networks. Finally, we develop a variety of biomimetic systems to reproduce and analyze the behaviors observed in the cell. This work requires a strong interdisciplinarity, at the crossroads of biology, chemistry and physics.
Our results allow us to propose a simple and efficient model of how life could generate new functions through the use of new actin isoforms.
A multi-disciplinary collaboration between the team of Alphée Michelot and the team of Olivia du Roure and Julien Heuvingh at the ESPCI publishes in Plos Biology a study demonstrating that the mechanical stiffness of endocytic actin patches correlates tightly with endocytosis efficiency.
The team of Alphée Michelot publishes in Plos Biology a study demonstrating how cells control the size of multiple actin networks within a common cytoplasm.