Key result
Partial titin degradation increases sarcomere length nonuniformities after stretch and reduces active and passive stresses.
This basic science study demonstrates that titin plays a critical role in preventing sarcomere overstretching during active stretch, which has implications for understanding mechanisms of muscle injury.
Titin supports sarcomere stability during active stretch in myofibrils; leaves open relevance to in vivo muscle injury or human disease.
The aim of this study was to determine the role of titin in preventing the development of sarcomere length nonuniformities following activation and after active and passive stretch by determining the effect of partial titin degradation on sarcomere length nonuniformities and force in passive and active myofibrils. Selective partial titin degradation was performed using a low dose of trypsin. Myofibrils were set at a sarcomere length of 2.4 µm and then passively stretched to sarcomere lengths of 3.4 and 4.4 µm. In the active condition, myofibrils were set at a sarcomere length of 2.8 µm, activated, and actively stretched by 1 µm/sarcomere. The extent of sarcomere length nonuniformities was calculated for each sarcomere as the absolute difference between sarcomere length and the mean sarcomere length of the myofibril. Our main finding is that partial titin degradation does not increase sarcomere length nonuniformities after passive stretch and activation compared with when titin is intact but increases the extent of sarcomere length nonuniformities after active stretch. Furthermore, when titin was partially degraded, active and passive stresses were substantially reduced. These results suggest that titin plays a crucial role in actively stretched myofibrils and is likely involved in active and passive force production.
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Joumaa et al. (2018) studied Preclinical myofibril model (rabbit psoas muscle) (n=4). Partial titin degradation (trypsin) vs. Titin-intact myofibrils was evaluated on Extent of sarcomere length non-uniformities after active stretch. Partial titin degradation increased the extent of sarcomere length nonuniformities after active stretch and substantially reduced active and passive stresses compared to intact myofibrils.
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