5.2.5. The Radial Growth of Myofibers—Closing Remarks

As we have discussed, a substantial body of evidence indicates that the mechanical load-induced radial growth of myofibers is mediated by a proportional increase in the force-generating and non-force-generating elements. The force-generating elements are contained within the myofibrils, and the myofibrils account for ≈80% of the myofiber CSA. Thus, it can be argued that the bulk of the radial growth is driven by an expansion of the myofibrils. However, whether this expansion is due to hypertrophy of the individual myofibrils and/or myofibril hyperplasia remains to be established. Based on our collective view of the literature, we propose that both processes are involved, and can be explained by a model that we have defined as the "myofibril expansion cycle". Specifically, as illustrated in Figure 11, the myofibril expansion cycle begins with the deposition of new myofilaments around the periphery of the pre-existing myofibrils, and results in myofibril hypertrophy. Once the myofibrils reach a critical size, they split and subsequently form two smaller daughter myofibrils. The daughter myofibrils are then able to enter another round of the cycle, and the cycle repeats until the radial growth of the myofiber has commenced. Clearly, our model is based on an integration of hypotheses that were proposed more than 40 years ago, and as emphasized throughout this section, the validity of these hypotheses have not been rigorously tested. Fortunately, the technologies that are needed to test these hypotheses are now available. Thus, we hope that this section will help to inspire new investigations into this seemingly forgotten, yet critically important aspect of skeletal muscle biology.

**Figure 11.** Illustration of the proposed "Myofibril Expansion Cycle".
