The skeletal muscle : a mechanically sensitive tissue. Implications for muscle dystrophy

Orateur : Catherine COIRAULT (Sorbonne University, Paris)

Since 2008, my group is focusing on the mechanobiology defects in muscular disorders. Our rationale is that whereas the primary function of skeletal muscle is to produce force and movement, mechanical forces in turn are critical to control muscle cell decisions and tissue homeostasis. We aim to explore how mechanical stress affect muscle mass and function in normal and pathological conditions. Recent studies demonstrate that nuclear envelope proteins including A-type lamins, are critical for the cell responses to mechanical cues. We thus aimed to determine whether mechanosensing defects contribute to the pathophysiology of muscular dystrophies related to mutations in nuclear envelop proteins. Using 3D cellular model we set up (Chiron et al. 2012), we revealed defective mechanosensing of human lamin mutant myoblasts due to abnormal YAP signaling, and emphasized the crucial role of the biophysical attributes of the cellular microenvironment (Bertrand et al 2014). We investigated the effects of lamin and NESPRIN-1 mutations on the dynamic response of cell-matrix adhesion, cytoskeleton components, nuclear deformations, and mechano-transduction signaling (Schwartz/Fischer et al, 2017). More recently, we investigated the role of lamin in skeletal muscle plasticity on the one hand, and the nuclear mechanisms contributing to defective YAP signaling on the other hand.

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