Diffusion and physical constraints limit oxidative capacity, capillary supply and size of muscle fibres in mice and humans

Degens, Hans ORCID: https://orcid.org/0000-0001-7399-4841, Messa, Guy A. M., Tallis, Jason ORCID: https://orcid.org/0000-0001-8904-2693, Bosutti, Alessandra ORCID: https://orcid.org/0000-0002-8651-818X, Venckunas, Tomas, Adeniran, Ismail ORCID: https://orcid.org/0000-0002-9775-3249, Wüst, Rob C. I. ORCID: https://orcid.org/0000-0003-3781-5177 and Hendrickse, Paul W. ORCID: https://orcid.org/0000-0003-2769-7816 (2025) Diffusion and physical constraints limit oxidative capacity, capillary supply and size of muscle fibres in mice and humans. Experimental Physiology. ISSN 1469-445X

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Abstract

It has been suggested that angiogenesis during skeletal muscle fibre hypertrophy allows escape from the ‘size constraint’, which is the inverse relationship between oxidative capacity and muscle fibre cross‐sectional area (FCSA). It is, however, not known whether there are any limitations to the combinations of FCSA, oxidative capacity and capillary supply to an individual fibre. We determined the FCSA, oxidative capacity and capillary supply to fibres from highly resistance‐trained men before and after superimposed endurance training, recreationally active men and women, and different mouse muscles. Both the oxidative capacity and the number of capillaries around a fibre (CAF) per FCSA (CAF/FCSA) showed an upper limit at each FCSA, irrespective of species, muscle origin or training status. The upper limit of fibre oxidative capacity was likely determined by diffusion constraints. The upper limit of CAF/FCSA was determined by physical constraints where (i) there is no further reduction in maximal diffusion distance to the core of a fibre beyond a CAF of 2, and (ii) the reduction in fibre area supplied by a capillary diminishes exponentially with an increase in CAF. The calculated upper limits of oxidative capacity and CAF/FCSA of a fibre of a given FCSA were linearly related. Irrespective of species, sex, muscle of origin and training status, our data indicate that diffusion limitations and physical limitations to capillary placement around a fibre place an upper limit on the oxidative capacity and capillary supply to a fibre of a given size, respectively.