Scaling of nuclear numbers and their spatial arrangement in skeletal muscle cell size regulation

Figures

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  FIGURE 1:. Intracellular transportation of macromolecules. Active transport along the cytoskeleton relies on the molecular motor protein transporting the cargo. Kinesins moving along microtubules typically move at a speed of 1 μm/s (Pilling et al., 2006), while myosin V moves at a speed of 3 μm/s (Schott et al., 2002). Diffusion time scales to the square of the distance traveled, causing diffusive transport of myoglobin within a fiber of the EDL muscle to be faster than actin-mediated transport for distances less than 25 μm and less than 75 μm relative to transportation along microtubules (Hansson et al., 2020b).

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  FIGURE 2:. Nuclear number scales in direct proportion to the surface area. (Ai) DNA content (nuclear number) regressed on fiber volume displays a sublinear relationship with a scaling parameter close to two-thirds. This results in a scaling where the fiber volume per nucleus increases sublinearly as the fiber grows larger (Aii). (B) On the contrary, there is a linear relationship between the fiber surface area and DNA content (nuclear number), causing the surface area per nucleus to be constant as the volume of the fiber increases (Bii), which may signify an interdependence between the plasma membrane and myonuclear productivity (see text for further information).

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  FIGURE 3:. Myonuclear plasticity space. The protein content for each gene can be achieved by combining the transcription and translation rates of mRNA and proteins, respectively, as well as their corresponding decay rates. The decay rates for mRNA (Dm) and protein (Dp) are the sum of their degradation rates and the dilution at a rate of h-1 during the growth of muscle fibers. Activation and signaling of growth pathways from the extracellular space can modulate each of these microstates, causing an unlimited number of ways to cross-combine the four microstates coupled to each of the numerous proteins to maintain steady-state fiber size (grand macrostate). For example, signaling via myostatin leads to activation of the Smad2/3 pathway, causing overall proteolysis within muscle fibers (Sartori et al., 2009), and thus influences Dp, while Sp and Dp are regulated by the extracellular cues mediated by the IGF-1 that leads to intracellular activation of the Akt/mTOR pathway that causes a net protein accumulation by promoting protein synthesis and inhibiting proteolysis (Schiaffino and Mammucari, 2011).

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  FIGURE 4:. Growth rates in muscle fibers are inversely proportional to the cytoplasmic volume. The growth rates within muscle fibers during development or overload-induced hypertrophy are proportional to the nuclear number, causing the fiber with greater DNA content (green) to reach larger sizes compared with the fiber with lesser DNA content (orange). Theoretically, fibers stop growing when certain growth factors become too diluted.