MBI investigators Benoit Ladoux and Pascal Hersen reveal the dynamic relationship between cellular forces and acto-myosin contractility in 3D-environments
Most tissue cells evolve in vivo in a three-dimensional (3D) microenvironments that include complex topographical patterns. Cells exert contractile forces to adhere and migrate through the extra-cellular matrix (ECM). Although cell mechanics has been extensively studied on 2D-surfaces, there are too few approaches that give access to the traction forces that are exerted in 3D environments. In the new issue of Lab on Chip, Pascal Hersen, Benoit Ladoux (both visiting scientists at the MBI) and colleagues describe an approach to measure dynamically the contractile forces exerted by fibroblasts while they spread within arrays of large flexible micropillars coated with ECM proteins.
Contrary to very dense arrays of microposts, the density of the micropillars has been chosen to promote cell adhesion in between the pillars. Cells progressively impale onto the micropatterned substrate. They first adhere on the top of the pillars without applying any detectable forces. Then, they spread along the pillars sides, spanning between the elastic micropillars and applying large forces on the substrate. Interestingly, the architecture of the actin cytoskeleton and of the adhesion complexes vary over time as cells pull on the pillars. In particular, we observed less stress fibers than for cells spread on flat surfaces. However, prominent actin stress fibers are observed at cell edges surrounding the micropillars. They generate increasing contractile forces during cells spreading.
Taken together, these findings highlight the dynamic relationship between cellular forces and acto-myosin contractility in 3D-environments, and the influence of cytoskeletal network mechanics on cell shape as well as the importance of cell-ECM contact area in the generation of traction forces.
Pascal Hersen is a visiting scientist at National University of Singapore. His research interests are biophysics, systems biology, microbiology, fluid mechanics, geomorphology, and interdisciplinary sciences.
Benoit Ladoux is a principal investigator at the Mechanobiology Institute, Singapore. His research areas include epithelial cell migration, microfabrication for cell mechanics, the influence of mechanical environments on cell functions, and mechanotransduction. Ladoux has initiated pluridisciplinary collaborations between French institutes as well as developing several collaborations with well-established international institutions such as IBEC (Spain), Harvard, Columbia, Carnegie Mellon (USA) and the MBI at NUS.
Learn more about the work done at the Living Organisms & Microfabrication Laboratory.