Benoit Ladoux’s latest findings on mechanosensing and cell substrate stiffness in PNAS

Research led by Prof Ladoux, principal investigator at MBI and the Universite Paris Diderot, investigates fibroblast cell migration using micro- and nano-fabrication techniques to manipulate the mechanical and chemical microenvironments cells find themselves in. Using this system alongside live cell imaging, Ladoux and colleagues are able to directly measure the forces at play during cell migration and how they affect cell adhesion and motility. Read the abstract here.

The Research

A rat embryonic fibroblast of the REF52 cell line spreading out on a bed of micropillars.

Research carried out in the Ladoux lab approaches mechanobiology from a biophysical viewpoint, marrying together the biology of cell motility with the physics of designing cellular microenvironments.

Prof Ladoux, with a background in single molecule biophysics and microfabrication, has developed original systems to control and measure mechanical interactions of cells during migration. Building on this work, first established whilst at the Universite Paris Diderot, Prof Ladoux continues to probe cellular mechanics with the aid of MBIs in-house Nano- and Micro-fabrication Core.

Recent Findings

Latest results from the Ladoux lab published in PNAS, entitled Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness, reveal that traction forces between a cell and its underlying substrate build faster on substrates of greater stiffness. Furthermore, forces detected at sites of adhesion were shown to be highly dependent on substrate stiffness. This was exemplified by the detection of different forces at focal adhesions that were of the same size but lying on substrates of differing rigidities.

A mouse embryonic fibroblast of the 3T3 cell line, plated on micropillars of varying sizes, produced in-house at MBI.

Together with modeling results based on active gel theory, Ladoux and colleagues demonstrate that the ability of a cell to sense the rigidity of its environment is facilitated by a large-scale mechanosensing mechanism originating from the cytoskeleton, rather than a local mechanism restricted to focal adhesions.

Experiments with cells plated on substrates with a rigidity boundary, showed they generally migrated towards stiffer substrates, within a limited rigidity range.

These findings illustrate that the stress-rigidity function between cells and their substrates relates to the larger mechanosensory system of the cytoskeleton. This holds importance for future studies into the affect of substrate stiffness on processes such as stem cell differentiation and tumour formation.

Learn more about Prof Ladoux’s research.