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Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase.

ABSTRACT: The molecular origin of the action of the F(0) proton gradient-driven rotor presents a major puzzle despite significant structural advances. Although important conceptual models have provided guidelines of how such systems should work, it has been challenging to generate a structure-based molecular model using physical principles that will consistently lead to the unidirectional proton-driven rotational motion during ATP synthesis. This work uses a coarse-grained (CG) model to simulate the energetics of the F(0)-ATPase system in the combined space defined by the rotational coordinate and the proton transport (PTR) from the periplasmic side (P) to the cytoplasmic side (N). The model establishes the molecular origin of the rotation, showing that this effect is due to asymmetry in the energetics of the proton path rather than only the asymmetry of the interaction of the Asp on the c-ring helices and Arg on the subunit-a. The simulation provides a clear conceptual background for further exploration of the electrostatic basis of proton-driven mechanochemical systems.

SUBMITTER: Mukherjee S

PROVIDER: S-EPMC3443130 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase.

Mukherjee Shayantani S Warshel Arieh A

Proceedings of the National Academy of Sciences of the United States of America 20120827 37

The molecular origin of the action of the F(0) proton gradient-driven rotor presents a major puzzle despite significant structural advances. Although important conceptual models have provided guidelines of how such systems should work, it has been challenging to generate a structure-based molecular model using physical principles that will consistently lead to the unidirectional proton-driven rotational motion during ATP synthesis. This work uses a coarse-grained (CG) model to simulate the energ ...[more]

PMID: 22927379

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Project description:Heterogeneous intercellular coupling plays a significant role in mechanical and electrical signal transmission in the heart. Although many studies have investigated the electrical signal conduction between myocytes and nonmyocytes within the heart muscle tissue, there are not many that have looked into the mechanical counterpart. This study aims to investigate the effect of substrate stiffness and the presence of cardiac myofibroblasts (CMFs) on mechanical force propagation across cardiomyocytes (CMs) and CMFs in healthy and heart-attack-mimicking matrix stiffness conditions. The contractile forces generated by the CMs and their propagation across the CMFs were measured using a bio-nanoindenter integrated with fluorescence microscopy for fast calcium imaging. Our results showed that softer substrates facilitated stronger and further signal transmission. Interestingly, the presence of the CMFs attenuated the signal propagation in a stiffness-dependent manner. Stiffer substrates with CMFs present attenuated the signal ∼24-32% more compared to soft substrates with CMFs, indicating a synergistic detrimental effect of increased matrix stiffness and increased CMF numbers after myocardial infarction on myocardial function. Furthermore, the beating pattern of the CMF movement at the CM-CMF boundary also depended on the substrate stiffness, thereby influencing the waveform of the propagation of CM-generated contractile forces. We performed computer simulations to further understand the occurrence of different force transmission patterns and showed that cell-matrix focal adhesions assembled at the CM-CMF interfaces, which differs depending on the substrates stiffness, play important roles in determining the efficiency and mechanism of signal transmission. In conclusion, in addition to substrate stiffness, the degree and type of cell-cell and cell-matrix interactions, affected by the substrate stiffness, influence mechanical signal conduction between myocytes and nonmyocytes in the heart muscle tissue.

Dataset Information

Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase.

Publications

Realistic simulations of the coupling between the protomotive force and the mechanical rotation of the F0-ATPase.

Similar Datasets

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