The effect of deuterium oxide on the stability of the collagen model peptides H‐(Pro‐Pro‐Gly)<sub>10</sub>‐OH, H‐(Gly‐Pro‐4(R)Hyp)<sub>9</sub>‐OH, and Type I collagen

Mizuno, Kazunori; Bächinger, Hans Peter

doi:10.1002/bip.21305

Cited by 10 publications

(15 citation statements)

References 43 publications

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“…This may indicate that water is indeed needed to keep the characteristic configuration of collagen molecules in microfibrils, in agreement with earlier work on collagen-like peptides at the single molecule scale where a greater level of disorder and loss of H-bonding was found in vacuum studies [30]. Nevertheless, more in-depth studies of this issue for example with Replica Exchange Molecular Dynamics, along with experimental validation, will be necessary, combined with further experimental work [51]. Overall our model shows good quantitative agreement with available experimental structural data of collagen microfibrils.…”

Section: Resultssupporting

confidence: 83%

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Gautieri

Vesentini²,

Redaelli³

et al. 2011

Nano Lett.

610

488

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Abstract:Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to connective tissues. Collagen is also the dominating material in the extracellular matrix (ECM) and is thus crucial for cell differentiation, growth and pathology. However, fundamental questions remain with respect to the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility and nonlinear mechanical response. By using x-ray diffraction data of a collagen fibril reported by Orgel et al.(Proceedings of the National Academy of Sciences USA, 2006) in combination with protein structure identification methods, here we present an experimentally validated model of the nanomechanics of a collagen microfibril that incorporates the full biochemical details of the amino acid sequence of the constituting molecules. We report the analysis of its mechanical properties under different levels of stress and solvent conditions, using a full-atomistic force field including explicit water solvent. Mechanical testing of hydrated collagen microfibrils yields a Young's modulus of ≈300 MPa at small and ≈1.2 GPa at larger deformation in excess of 10% strain, in excellent agreement with experimental data. Dehydrated, dry collagen microfibrils show a significantly increased Young's modulus of ≈1.8 to 2.25 GPa (or ≈6.75 times the modulus in the wet state) owing to a much tighter molecular packing, in good agreement with experimental measurements (where an increase of the modulus by ≈9 times was found). Our model demonstrates that the unique mechanical properties of collagen microfibrils can be explained based on their hierarchical structure, where deformation is mediated through mechanisms that operate at different hierarchical levels. Key mechanisms involve straightening of initially disordered and helically twisted molecules at small strains, followed by axial stretching of molecules, and eventual molecular uncoiling at extreme deformation. These mechanisms explain the striking difference of the modulus of collagen fibrils compared with single molecules, which is found in the range of 4.8±2 GPa or ≈10-20 times greater. These findings corroborate the notion that collagen tissue properties are highly scale dependent and nonlinear elastic, an issue that must be considered in the development of models that describe the interaction of cells with collagen in the extracellular matrix. A key impact the atomistic model of collagen microfibril mechanics reported here is that it enables the bottom-up elucidation of structure-property relationships in the broader class of collagen materials such as tendon or bone, including studies in the context of genetic disease where the incorporation of biochemical, genetic details in material models of connective tissue is essential.

show abstract

Section: Resultssupporting

confidence: 83%

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Gautieri

Vesentini²,

Redaelli³

et al. 2011

Nano Lett.

610

488

View full text Add to dashboard Cite

show abstract

“…A complete set of thermodynamic parameters for the N‐terminal domain of ribosomal protein L9 (56 residues) and hen egg white lysozyme (129 residues) is reported in Table . Similar stabilizing effects have also been obtained for collagen model peptides, and elastin‐like polypeptides …”

Section: Introductionsupporting

confidence: 75%

Effect of heavy water on the conformational stability of globular proteins

Pica

Graziano

2017

Biopolymers

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It is well established from the experimental point of view that the native state of globular proteins is more stable in heavy water than in water. No robust explanation, however, has been provided up to now. The application of the theoretical approach, originally devised to rationalize the general occurrence of cold denaturation, indicates that the magnitude of the solvent-excluded volume effect is slightly smaller in heavy water than in water and cannot explain the observed protein stabilization. The latter has to be due to the strength of protein-water van der Waals attractions which are weaker in heavy water due to the smaller molecular polarizability of D O compared with that of H O molecules. Since protein-water van der Waals attractions occur more in the denatured than in the native state, this contribution leads to a stabilization of the latter through a destabilization of the former.

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Section: Resultssupporting

confidence: 82%

Hierarchical nanomechanics of collagen microfibrils

et al. 2010

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Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to connective tissues. Collagen is also the dominating material in the extracellular matrix (ECM) and is thus crucial for cell differentiation, growth and pathology. However, fundamental questions remain with respect to the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility and nonlinear mechanical response. By using x-ray diffraction data of a collagen fibril reported by Orgel et al. (Proceedings of the National Academy of Sciences USA, 2006) in combination with protein structure identification methods, here we present an experimentally validated model of the nanomechanics of a collagen microfibril that incorporates the full biochemical details of the amino acid sequence of the constituting molecules. We report the analysis of its mechanical properties under different levels of stress and solvent conditions, using a full-atomistic force field including explicit water solvent. Mechanical testing of hydrated collagen microfibrils yields a Young's modulus of ≈300 MPa at small and ≈1.2 GPa at larger deformation in excess of 10% strain, in excellent agreement with experimental data. Dehydrated, dry collagen microfibrils show a significantly increased Young's modulus of ≈1.8 to 2.25 GPa (or ≈6.75 times the modulus in the wet state) owing to a much tighter molecular packing, in good agreement with experimental measurements (where an increase of the modulus by ≈9 times was found). Our model demonstrates that the unique mechanical properties of collagen microfibrils can be explained based on their hierarchical structure, where deformation is mediated through mechanisms that operate at different hierarchical levels. Key mechanisms involve straightening of initially disordered and helically twisted molecules at small strains, followed by axial stretching of molecules, and eventual molecular uncoiling at extreme deformation. These mechanisms explain the striking difference of the modulus of collagen fibrils compared with single molecules, which is found in the range of 4.8±2 GPa or ≈10-20 times greater. These findings corroborate the notion that collagen tissue properties are highly scale dependent and nonlinear elastic, an issue that must be considered in the development of models that describe the interaction of cells with collagen in the extracellular matrix. A key impact the atomistic model of collagen microfibril mechanics reported here is that it enables the bottom-up elucidation of structure-property relationships in the broader class of collagen materials such as tendon or bone, including studies in the context of genetic disease where the incorporation of biochemical, genetic details in material models of connective tissue is essential.

show abstract

The effect of deuterium oxide on the stability of the collagen model peptides H‐(Pro‐Pro‐Gly)₁₀‐OH, H‐(Gly‐Pro‐4(R)Hyp)₉‐OH, and Type I collagen

Cited by 10 publications

References 43 publications

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Effect of heavy water on the conformational stability of globular proteins

Hierarchical nanomechanics of collagen microfibrils

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The effect of deuterium oxide on the stability of the collagen model peptides H‐(Pro‐Pro‐Gly)10‐OH, H‐(Gly‐Pro‐4(R)Hyp)9‐OH, and Type I collagen

Cited by 10 publications

References 43 publications

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Effect of heavy water on the conformational stability of globular proteins

Hierarchical nanomechanics of collagen microfibrils

Contact Info

Product

Resources

About

The effect of deuterium oxide on the stability of the collagen model peptides H‐(Pro‐Pro‐Gly)₁₀‐OH, H‐(Gly‐Pro‐4(R)Hyp)₉‐OH, and Type I collagen