Active Force Augmentation for Physiologically Relevant Stretches in Myofibrils and Mechanically Isolated Sarcomeres

Abstract

We reported previously that forces in actively stretched myofibrils and sarcomeres were up to four times greater than forces in passively stretched myofibrils at sarcomere lengths >4μm. These increased forces were independent of actin-myosin based cross-bridge forces and were absent when titin was eliminated. Here, we demonstrate that such force augmentation also occurs for physiologically relevant sarcomere lengths (2.4-4.0μm). Actin-myosin based cross-bridge forces and non cross-bridge based forces were distinguished by assuming that sarcomeres reached a steady-state cross-bridge distribution in the first 0.4μm of stretch. The forces due to stretching could then be calculated and added to the passive forces measured during passive stretching (Figure 1) to obtain the expected forces during active stretching. Subtracting the expected from the experimentally measured forces during active stretching, the force augmentation was obtained. Mean force augmentation towards the end stretching reached values in excess of the mean maximal active isometric forces at optimal sarcomere length, suggesting that force augmentation not associated with actin-myosin based cross-bridge forces is highly relevant in actively stretched myofibrils and isolated sarcomeres.