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Simulation of the mechanical strength of a single collagen molecule.

ABSTRACT: We perform atomistic simulations on a single collagen molecule to determine its intrinsic molecular strength. A tensile pull simulation to determine the tensile strength and Young's modulus is performed, and a simulation that separates two of the three helices of collagen examines the internal strength of the molecule. The magnitude of the calculated tensile forces is consistent with the strong forces of bond stretching and angle bending that are involved in the tensile deformation. The triple helix unwinds with increasing tensile force. Pulling apart the triple helix has a smaller, oscillatory force. The oscillations are due to the sequential separation of the hydrogen-bonded helices. The force rises due to reorienting the residues in the direction of the separation force. The force drop occurs once the hydrogen bond between residues on different helices break and the residues separate.

SUBMITTER: in 't Veld PJ

PROVIDER: S-EPMC2426635 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Simulation of the mechanical strength of a single collagen molecule.

in 't Veld Pieter J PJ Stevens Mark J MJ

Biophysical journal 20080321 1

We perform atomistic simulations on a single collagen molecule to determine its intrinsic molecular strength. A tensile pull simulation to determine the tensile strength and Young's modulus is performed, and a simulation that separates two of the three helices of collagen examines the internal strength of the molecule. The magnitude of the calculated tensile forces is consistent with the strong forces of bond stretching and angle bending that are involved in the tensile deformation. The triple h ...[more]

PMID: 18359794

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Project description:The bacterial pathogen Staphylococcus aureus expresses a variety of cell surface adhesion proteins that bind to host extracellular matrix proteins. Among these, the collagen (Cn)-binding protein Cna plays important roles in bacterium-host adherence and in immune evasion. While it is well established that the A region of Cna mediates ligand binding, whether the repetitive B region has a dedicated function is not known. Here, we report the direct measurement of the mechanical strength of Cna-Cn bonds on living bacteria, and we quantify the antiadhesion activity of monoclonal antibodies (MAbs) targeting this interaction. We demonstrate that the strength of Cna-Cn bonds in vivo is very strong (~1.2 nN), consistent with the high-affinity "collagen hug" mechanism. The B region is required for strong ligand binding and has been found to function as a spring capable of sustaining high forces. This previously undescribed mechanical response of the B region is of biological significance as it provides a means to project the A region away from the bacterial surface and to maintain bacterial adhesion under conditions of high forces. We further quantified the antiadhesion activity of MAbs raised against the A region of Cna directly on living bacteria without the need for labeling or purification. Some MAbs are more efficient in blocking single-cell adhesion, suggesting that they act as competitive inhibitors that bind Cna residues directly involved in ligand binding. This report highlights the role of protein mechanics in activating the function of staphylococcal adhesion proteins and emphasizes the potential of antibodies to prevent staphylococcal adhesion and biofilm formation.ImportanceCna is a collagen (Cn)-binding protein from Staphylococcus aureus that is involved in pathogenesis. Currently, we know little about the functional role of the repetitive B region of the protein. Here, we unravel the mechanical strength of Cna in living bacteria. We show that single Cna-Cn bonds are very strong, reflecting high-affinity binding by the collagen hug mechanism. We discovered that the B region behaves as a nanospring capable of sustaining high forces. This unanticipated mechanical response, not previously described for any staphylococcal adhesin, favors a model in which the B region has a mechanical function that is essential for strong ligand binding. Finally, we assess the antiadhesion activity of monoclonal antibodies against Cna, suggesting that they could be used to inhibit S. aureus adhesion.

Project description:BACKGROUND:Regular loading of tendons may counteract the negative effects of aging. However, the influence of strength training loading magnitude on tendon mechanical properties and its relation to matrix collagen content and collagen cross-linking is sparsely described in older adults. The purpose of the present study was to compare the effects of moderate or high load resistance training on tendon matrix and its mechanical properties. METHODS:Seventeen women and 19 men, age 62-70?years, were recruited and randomly allocated to 12?months of heavy load resistance training (HRT), moderate load resistance training (MRT) or control (CON). Pre- and post-intervention testing comprised isometric quadriceps strength test (IsoMVC), ultrasound based testing of in vivo patellar tendon (PT) mechanical properties, MRI-based measurement of PT cross-sectional area (CSA), PT biopsies for assessment of fibril morphology, collagen content, enzymatic cross-links, and tendon fluorescence as a measure of advanced glycation end-products (AGEs). RESULTS:Thirty three participants completed the intervention and were included in the data analysis. IsoMVC increased more after HRT (+?21%) than MRT (+?8%) and CON (+?7%) (p?<?0.05). Tendon stiffness (p?<?0.05) and Young's modulus (p?=?0.05) were also differently affected by training load with a reduction in CON and MRT but not in HRT. PT-CSA increased equally after both MRT and HRT. Collagen content, fibril morphology, enzymatic cross-links, and tendon fluorescence were unaffected by training. CONCLUSION:Despite equal improvements in tendon size after moderate and heavy load resistance training, only heavy. load training seemed to maintain tendon mechanical properties in old age. The effect of load magnitude on tendon biomechanics was unrelated to changes of major load bearing matrix components in the tendon core. The study is a sub-study of the LISA study, which was registered at http://clinicaltrials.gov (NCT02123641) April 25th 2014.

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Simulation of the mechanical strength of a single collagen molecule.

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Simulation of the mechanical strength of a single collagen molecule.

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