Unidirectional Brownian motion observed in an in silico single molecule experiment of an actomyosin motor

Abstract

The actomyosin molecular motor, the motor composed of myosin II and actin filament, is responsible for muscle contraction, converting chemical energy into mechanical work. Although recent single molecule and structural studies have shed new light on the energy-converting mechanism, the physical basis of the molecular-level mechanism remains unclear because of the experimental limitations. To provide a clue to resolve the controversy between the lever-arm mechanism and the Brownian ratchet-like mechanism, we here report an in silico single molecule experiment of an actomyosin motor. When we placed myosin on an actin filament and allowed myosin to move along the filament, we found that myosin exhibits a unidirectional Brownian motion along the filament. This unidirectionality was found to arise from the combination of a nonequilibrium condition realized by coupling to the ATP hydrolysis and a ratchet-like energy landscape inherent in the actin-myosin interaction along the filament, indicating that a Brownian ratchet-like mechanism contributes substantially to the energy conversion of this molecular motor. M olecular machines in living organisms are nanometer-sized small systems working robustly and efficiently in the presence of the severely disturbing thermal noises. Furthermore, in the case of the molecular motors, the energy supplied by the hydrolysis of adenosine triphosphate (ATP), which is to be converted to the mechanical work, is only an order of magnitude larger than the thermal energy at room temperature (∼20k B T), and hence it seems likely that the molecular machines harness the thermal noise, instead of suppressing it as the human-made machines do (1). This distinct feature of the molecular machines should arise from the atomic structures of the constituent proteins, which is reflected in the current focus of interest in the structural aspect of the molecular machines. However, it should be remembered that the structural aspect is not everything but is inseparably linked to the dynamical and energetical aspects. Therefore, a unified description of structure, dynamics, and energetics is the step necessary to understand the molecular-level physical principle of how the molecular machines work.The actomyosin molecular motor, the system composed of myosin II and actin molecules, is responsible for muscle contraction, and is the most extensively studied molecular motor. It has been shown by single molecule experiments (SME) that a single myosin molecule and an actin filament (polymerized actin) constitute the minimal force-generating unit of this motor (2-4) (see Fig. 1A). Although SME has been a powerful approach to study the dynamical aspect of the force-generating unit (2-4), the limitation of the spatiotemporal resolution of SME has inhibited us from developing the full atomistic picture of the force-generating process. On the other hand, since the currently available high-resolution structures of myosin (5-7) are those obtained in the crystalline environment and in the absence of actin, it remains unc...

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Entropic potential field formed for a linear-motor protein near a filament: Statistical-mechanical analyses using simple models

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Asymmetric transportation induced by thermal noise at the nanoscale

“…In 1997, Kelly et al [22,23] designed a molecule containing triptycene with helicenes, and observed spontaneous unidirectional rotations of the triptycene over a short time period. Takano et al placed myosin on an actin filament and allowed myosin to move along the filament, and found that myosin exhibits a unidirectional Brownian motion along the filament [8]. Here we show that the thermal noise may drive particles into unidirectional motion in nanoscale systems, based on the break from spatial inversion symmetry and the underlying physics if we consider the non-white behavior of the thermal noise in a nanoscale system.…”

“…observed in the systems that break the spatial inversion symmetry, particularly with nanoand biosystems [1][2][3][4][5][6][7][8][9][10][11][12].…”

“…The conventional ratchet theory, initiated from Smoluchowski in 1912 [13] and Feynman later [14], indicate that asymmetric transportation can exist only under the existence of an additional stochastic perturbation with long-range time correlation [15][16][17][18][19][20][21], while the thermal noise is regarded as white noise with negligible time correlation; however, in some nanoscale systems external fluctuations have not been actively applied [5,[8][9][22][23]. Nanoscale systems usually display behavior different from bulk systems.…”