Grant: Operating Grant

When active muscles are repeatedly stretched, they become injured and lose the ability to produce force. Although observations on stretch-induced muscle injuries are abundant, the origin for these injuries remains a matter of debate. The most prominent theory is the idea that the smallest contractile units in muscles (the sarcomeres) become over-stretched (disrupted), thereby loosing the ability to produce force. This is thought to occur because sarcomeres are either over-stretched or not activated properly and thus fail. In skeletal muscles, the first theory prevails, while in heart muscle the second does. In the proposed research, we will study sarcomere disruption and contraction failure systematically in skeletal and heart muscles for the first time on the individual sarcomere level, thereby gaining novel information about the sub-cellular mechanisms of skeletal muscle injury and heart failure. We can perform these unique experiments because we have refined an approach to work with single myofibrils and mechanically isolated sarcomeres, and have invented a completely new approach to simulate contraction failure in selected sarcomeres of a myofibril. The results of this study will not only add basic knowledge to our understanding of how muscles contract and produce force, but will also provide first direct information on the effects of sarcomere disruption and contraction failure on skeletal muscle injury and heart failure.