Titin-dependent biomechanical feedback tailors sarcomeres to specialized muscle functions in insects

Sarcomeres are the universal contractile units of muscles that enable animals to move. Insect muscles display a remarkable functional diversity: they operate at extremely different contraction frequencies (ranging from ~1 to 1000 hertz) and amplitudes during flying, walking, and crawling. This is puzzling because sarcomeres are built from essentially the same actin-myosin components. Here, we address how functionally different sarcomeres are made. We show that the giant protein titin and the regulation of developmental contractility are key for the sarcomere specializations. I-band titin spans and determines the length of the sarcomeric I-band in a muscle type–specific manner. Unexpectedly, I-band titin also rules the length of the force-generating myosin filament using a feedback mechanism that is modulated by myosin contractility. We propose a model of how sarcomere specializations in insects are tuned, provide evidence for this model, and discuss its validity beyond insects.