Active And Passive Myofibrils Lengthened Beyond Acto-myosin Filament Overlap Produce Different Forces

Abstract

We stretched myofibrils actively and passively beyond myofilament overlap and measured forces. We expected active myofibrils stretched beyond myofilament overlap to produce the same force as equally long passively stretched myofibrils. Actively stretched myofibrils produced approximately four times more force than passively stretched myofibrils (Figure 1). Titin deletion with active and passive stretching resulted in complete force loss suggesting titin plays a crucial role in active and passive force production. Calcium activation and force inhibition through BDM reproduced the passive force curve, suggesting that titin and active force and not just Ca2+ activation was required for the large force of actively stretched myofibrils at lengths beyond myofilament overlap. Based on these results, we suggest that titin is a molecular spring whose stiffness is regulated by changes in effective length which in turn are controlled by force-dependent actin-titin interactions.