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Deciphering mechano-biology using super-resolution microscopy - Nature Cell Biology, July 2020

Deciphering mechano-biology using super-resolution microscopy - Nature Cell Biology, July 2020

Cell stretching is amplified by active actin remodeling to deform and recruit proteins in mechano-sensitive structures

Detection and conversion of mechanical forces into biochemical signals control cell functions during physiological and pathological processes. Mechano-sensing is based on protein deformations and reorganizations, yet the molecular mechanisms are still unclear. Using a cell stretching device compatible with super-resolution microscopy (SRM) and single protein tracking (SPT), we explored the nanoscale deformations and reorganizations of individual proteins inside mechano-sensitive structures. We achieved SRM after live stretching on intermediate filaments, microtubules and integrin adhesions. Simultaneous SPT and stretching showed that while integrins follow the elastic deformation of the substrate, actin filaments and talin also displayed lagged and transient inelastic responses associated with active acto-myosin remodeling and talin deformations. Capturing acute reorganizations of single-molecule during stretching showed that force-dependent vinculin recruitment is delayed and depends on the maturation of integrin adhesions. Thus, cells respond to external forces by amplifying transiently and locally cytoskeleton displacements enabling protein deformation and recruitment in mechano-sensitive structures.

Combination of live stretching with Super-Resolution Microscopy or Single Protein Tracking to study the mechanical properties of mechanosensitive structures and proteins. A) Live stretching combined with DNA-PAINT. Low resolution fluorescence image of vimentin-GFP in a fibroblast (left) on the stretching device before (green) and after (magenta) a 35% large stretching. DNA-PAINT super-resolution images of vimentin after 35% stretching (center and right). B) Live stretching combined with STED. Low resolution fluorescence image of Tubulin-GFP in a fibroblast (left) on the stretching device before (green) and after (magenta) 35% large stretching followed by rapid cell fixation. STED super-resolution images of tubulin labelled with ATTO-647N after 35% stretching (center and right). C) Projection of all talin-C-tdEos super-resolution intensity images of a trapeze-like pattern time-lapse, composed of stretch-plateau-relax phases (left). On the center, talin-C-tdEos kymographs generated from the trapeze-like pattern time-lapse (as shown in the left panel, dashed line). The magenta kymograph corresponds to the reference bead, and the green kymographs correspond to talin-C-tdEos displaying elastic (no unfolding) and inelastic responses (unfolding). On the right, a schematic representation of the acute mechanical response of talin.

Authors: Sophie Massou*, Filipe Nunes Vicente*, Franziska Wetzel*, Amine Mehidi, Dan Strehle, Cecile Leduc, Raphaël Voituriez, Olivier Rossier, Pierre, Nassoy and Gregory Giannone
* First co-authors

- Nature Cell Biology, DOI 10.1038/s41556-020-0548-2.
- Contacts IINS: Grégory Giannone and Filipe Nunes Vicente

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+ Cf. Bordeaux Neurocampus website here