Mapping muscle architecture

A reNEW Leiden team, led by Fanny Sage and Niels Geijsen, has revealed how skeletal muscles are organized at the tissue level. By combining RNA tomography and mass spectrometry imaging, the team mapped the spatial organization of muscle fibers, shedding light on how muscle types and metabolic activities are distributed within the tissue. This insight, published in Communications Biology, could shape approaches to muscle disease treatment by targeting specific fiber types and regions.

Skeletal muscle diversity
Although seemingly uniform, skeletal muscle is a surprisingly diverse network of long fibers, each composed of hundreds of non-dividing myonuclei that share a common cytoplasm. These fibers are categorized by their contraction speed and energy use. “Slow, oxidative muscle fibers, are good for endurance activities like marathons. They can last for a long time but contract relatively slowly,” explains first author Clara Martinez Mir. “In contrast, fast, glycolic fibers rely on glycolysis for quick bursts of activity like sprinting, but fatigue quickly.”

The study uncovered a striking pattern: fast glycolytic fibers located near the tendon connections, while central muscle regions contain more oxidative fibers. The team observed this consistent pattern across different muscle types, pointing to a fundamental structural organizational that is crucial for muscle function.

A muscle landscape
Previous work on isolated muscle fibers or biopsies lacked this whole-tissue-perspective. By mapping gene activity and metabolism across whole muscle tissues, the team has provided a new lens for examining muscle function and adaptation.

Understanding this complex muscle architecture opens new avenues for research into muscle health, aging, and disease. It is known that diseases like Duchenne muscular dystrophy and diabetes affect muscle fibers unevenly, but there has been limited knowledge on how these changes manifest spatially. “Our aim is to apply these insights to study how muscle tissue organization differs in disease contexts,” says Martinez Mir. “Our ultimate goal is to guide the development of targeted therapies that leverage this spatial knowledge to improve muscle function and resilience.”

The study exemplifies reNEW’s commitment to advancing cellular and tissue-level understanding, with applications that could transform the treatment of muscle-related diseases.