Fig. 5.

Schematic illustration explaining that the heart is an organ in which macro- and nano-operations are directly coupled through the long-range force produced by an assembly of molecular motors. At a nanoscopic level, an actomyosin motor, a stochastic nano-machine, produces a sliding force at random. In a sarcomere, an assembly of myofilaments, i.e., a bundle of the thick and the thin filaments, slides past to each other, resulting in the shortening of myofibrils, a series connection of sarcomeres, against the force (load) externally applied. As a result, cardiomyocytes, an assembly of myofibrils, and myocardium (Fig. 1), an assembly of cardiomyocytes, contract. Rhythmic contraction of heart occurs due to the coordinated contraction and relaxation cycle of myocardium constructing the heart outer and inner walls. Focusing on the force generation pathway, we call this “a feedforward regulation”. On the other hand, “a feedback regulation” pathway exists, i.e., the timing of heartbeat is controlled by electric impulse produced by pacemaker cells in a sinoatrial node. This signal is transferred to the myocardium through a conducting system. When cardiomyocytes at some region of heart begin to contract, those at the other region of heart will receive the stress due to the long-range force, resulting in the distortion of myofilaments and cross-bridges. This may cause the modulation of enzymatic activity of actomyosin motors and their regulation. Thus, we propose that a feedforward and feedback regulatory mechanism exists in heartbeat. In other words, there exists a chemo-mechanical feedback loop in the heartbeat. It means that heart is an organ in which macro- and nano-operations are directly coupled to each other