When you lift weights, your muscles grow bigger mainly because of the physical tugging and stretching they feel — and scientists think a special protein team (filamin-C and BAG3) might be the muscle’s internal detector that tells the cell to start growing, but we still don’t fully understand how it works.

Directly tests whether filamin-C or BAG3 knockout in human muscle cells abolishes mTORC1/Hippo/autophagy responses to mechanical stretch, without confounding systemic factors.

Determines whether loss of filamin-C or BAG3 in skeletal muscle blocks hypertrophy in response to resistance training in a living mammal with intact physiology.

Demonstrates real-time spatial-temporal coupling between mechanical loading and filamin-C-BAG3 complex formation and downstream signaling in human muscle in vivo.

Tests whether altering mechanical load (via eccentric vs concentric focus) differentially activates filamin-C-BAG3 signaling and correlates with hypertrophy in humans.

Determines whether naturally occurring human mutations in filamin-C or BAG3 impair mechanotransduction and muscle growth, providing human genetic evidence for the sensor hypothesis.