ART x SCIENCE 2025 #22
Fuse, Fire, Force: Making functional muscle models

Skeletal muscle disease affects individuals of all ages. Muscular dystrophy affects around 1 in 1000 children, while sarcopenia impacts up to 15% of elderly individuals. We use 2D and 3D in vitro muscle culture to improve our understanding of the mechanisms underlying both genetic and acquired muscle disease. This in turn allows us to identify new therapeutic targets for skeletal muscle diseases.

Body area Skeletal Muscle

Impact

For an organ such as muscle, measuring functional outputs is vital to understanding disease progression. Our lab measures physiologically relevant muscle functions such as contractile force in 3D tissues. We aim to make our models as similar to real muscle as possible, as the more relevant our 3D tissues are to actual tissue, the better we can predict how drugs will act in a patient’s muscle.

reNEW research

The Mills Lab has developed functional 3D skeletal muscle tissues which produce contractile force upon stimulation. We have developed culture conditions which improve their functional outputs, including contractile force, and increased expression of markers associated with muscle maturity. We use this system to investigate genetic muscle disease and muscle wasting associated with aging.

Image description

2D muscle fibres. Primary myoblasts differentiate and fuse to form myotubes which mature as they age. Here we see muscle fibres stained for ACTN2 which acts as a proxy for muscle fibre maturity. The bright yellow areas denote the more mature areas of the muscle fibre. The more mature the fibres are, the better they represent actual human tissue.

Credits

Dr Callum Dark, Senior Research Officer, Dr Tabitha Cree, Research Officer, Mills Lab, reNEW Melbourne.