Physical driving force of actomyosin motility based on the hydration effect

Abstract

We propose a driving force hypothesis based on previous thermodynamics, kinetics and structural data as well as additional experiments and calculations presented here on water-related phenomena in the actomyosin systems. Although Szent-Györgyi pointed out the importance of water in muscle contraction in 1951, few studies have focused on the water science of muscle because of the difficulty of analyzing hydration properties of the muscle proteins, actin, and myosin. The thermodynamics and energetics of muscle contraction are linked to the water-mediated regulation of protein-ligand and protein-protein interactions along with structural changes in protein molecules. In this study, we assume the following two points: (1) the periodic electric field distribution along an actin filament (F-actin) is unidirectionally modified upon binding of myosin subfragment 1 (M or myosin S1) with ADP and inorganic phosphate Pi (M.ADP.Pi complex) and (2) the solvation free energy of myosin S1 depends on the external electric field strength and the solvation free energy of myosin S1 in close proximity to F-actin can become the potential force to drive myosin S1 along F-actin. The first assumption is supported by integration of experimental reports. The second assumption is supported by model calculations utilizing molecular dynamics (MD) simulation to determine solvation free energies of a small organic molecule and two small proteins. MD simulations utilize the energy representation method (ER) and the roughly proportional relationship between the solvation free energy and the solvent-accessible surface area (SASA) of the protein. The estimated driving force acting on myosin S1 is as high as several piconewtons (pN), which is consistent with the experimentally observed force.

Physical pictures of rotation mechanisms of F1- and V1-ATPases: Leading roles of translational, configurational entropy of water

“…The ATP hydrolysis or synthesis reaction is tightly coupled to the rotation in the normal or inverse direction through the water-entropy effect. Our proposal is in line with the recent experimental results observed for actomyosin (Section 1) and the theoretical efforts (Amano et al, 2010;Suzuki et al, 2017;Kinoshita, 2018) showing that the force for moving myosin unidirectionally along F-actin is generated through the effect of hydration of actomyosin (see Supplementary Section S16 and Section 2.9 in the recently published book (Kinoshita, 2021a)). In one of the theoretical efforts (Suzuki et al, 2017), the force acting on S1 was estimated to be several piconewtons, as strong as the experimentally observed force.…”

“…Our proposal is in line with the recent experimental results observed for actomyosin (Section 1) and the theoretical efforts (Amano et al, 2010;Suzuki et al, 2017;Kinoshita, 2018) showing that the force for moving myosin unidirectionally along F-actin is generated through the effect of hydration of actomyosin (see Supplementary Section S16 and Section 2.9 in the recently published book (Kinoshita, 2021a)). In one of the theoretical efforts (Suzuki et al, 2017), the force acting on S1 was estimated to be several piconewtons, as strong as the experimentally observed force. The free energy of the system is variable depending on the conformation of actomyosin (i.e., structures, orientations, and positions of myosin and F-actin) or F 1 -ATPase.…”

On the functioning mechanism of an ATP-driven molecular motor

“…In the previous studies on actomyosin and F 1 -ATPase, the attention was focused on the conversion of free energy of the ATP hydrolysis to mechanical work and the critical role of water was not suitably taken into account (besides the papers by the author and coworkers, there is only one paper [17] showing the crucial importance of hydration of myosin and F-actin using an approach based on statistical mechanics; see [2] for a detailed discussion). Not only the proteins or protein complexes but also the aqueous solution of ATP, ADP, and Pi in which they are immersed forms the system.…”

My various thoughts on actin

“…I wonder if there is a point overlapping between the properties summarized in the Proceedings of Ciba Foundation Symposium 50 years ago ( Table 3 , [ 27 ]) and those presented by Uyeda and his colleagues in the Actin Symposium held in 2016 in Nagoya [ 28 , 29 ]. It was a great pleasure to see many presentations on various severing proteins of actin filaments, such as fragmin [ 24 ], gelsolin (e.g., [ 30 ]), villin (e.g., [ 31 ]), ADF/cofilin (e.g., [ 32 ]) and Pf ADF1 (e.g., [ 33 ]), and electron microscopic observations on actin polymers at this Actin Symposium (see [ 4 , 29 , 34 – 40 ]).…”