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Mapping Mechanical Force Propagation through Biomolecular Complexes.

ABSTRACT: Here we employ single-molecule force spectroscopy with an atomic force microscope (AFM) and steered molecular dynamics (SMD) simulations to reveal force propagation pathways through a mechanically ultrastable multidomain cellulosome protein complex. We demonstrate a new combination of network-based correlation analysis supported by AFM directional pulling experiments, which allowed us to visualize stiff paths through the protein complex along which force is transmitted. The results implicate specific force-propagation routes nonparallel to the pulling axis that are advantageous for achieving high dissociation forces.

SUBMITTER: Schoeler C

PROVIDER: S-EPMC4721519 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Mapping Mechanical Force Propagation through Biomolecular Complexes.

Schoeler Constantin C Bernardi Rafael C RC Malinowska Klara H KH Durner Ellis E Ott Wolfgang W Bayer Edward A EA Schulten Klaus K Nash Michael A MA Gaub Hermann E HE

Nano letters 20150819 11

Here we employ single-molecule force spectroscopy with an atomic force microscope (AFM) and steered molecular dynamics (SMD) simulations to reveal force propagation pathways through a mechanically ultrastable multidomain cellulosome protein complex. We demonstrate a new combination of network-based correlation analysis supported by AFM directional pulling experiments, which allowed us to visualize stiff paths through the protein complex along which force is transmitted. The results implicate spe ...[more]

PMID: 26259544

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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

Mapping Mechanical Force Propagation through Biomolecular Complexes.

Publications

Mapping Mechanical Force Propagation through Biomolecular Complexes.

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