The In Situ Supermolecular Structure of Type I Collagen

Orgel, Joseph P. R. O.; Miller, A.; Irving, Thomas C.; Fischetti, Robert F.; Hammersley, A. P.; Wess, Timothy James

doi:10.1016/s0969-2126(01)00669-4

Cited by 300 publications

(275 citation statements)

References 27 publications

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“…Our first observation is that the folded configuration is stable, according to the converging RMSD after 3 ns as depicted in Fig 3. This result suggests that the structure predicted by earlier x-ray diffraction [18] is indeed stable in our model, and provides a validation of the hypothesized geometry of the C-terminal telopeptides. Fig.…”

Section: Resultssupporting

confidence: 78%

“…Then, they are positioned in space by manual manipulation using Visual Molecular Dynamics (VMD) [20] in order to reach an approximate alignment with the C-terminus region. In the same fashion, the N-terminus region is juxtaposed to the C-terminus region in order to achieve an overlap of 30 nm, according to experimental data [18]. Consequently, the telopeptides are shaped so as to reach the particular pattern suggested in [18] as displayed in Fig.…”

Section: Molecular Structurementioning

confidence: 97%

“…Using x-ray diffraction on rat-tail tendon collagen fibrils, it was recently shown that the Cterminal cross-link occur between lysine 17 and lysine 87 in adjacent molecules, and more importantly, it was suggested that the telopeptide takes a folded configuration as shown in the schematic in Fig. 1 [18]. By utilizing these experimental advances as a guide, we build a full atomistic model of the entire overlap region of two collagen molecules, incorporating a covalent cross-link between the above mentioned lysine residues.…”

Section: Introductionmentioning

confidence: 99%

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Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen

Uzel

Buehler

2011

Journal of the Mechanical Behavior of Biomedical Materials

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ABSTRACT:Collagen is a key constituent in structural materials found in biology, including bone, tendon, skin and blood vessels. Here we report a first molecular level model of an entire overlap region of a C-terminal cross-linked type I collagen assembly and carry out a nanomechanical characterization based on large-scale molecular dynamics simulation in explicit water solvent. Our results show that the deformation mechanism and strength of the structure is greatly affected by the presence of the cross-link, and by the specific loading condition of how the stretching is applied. We find that the presence of a cross-link results in greater strength during deformation as complete intermolecular slip is prevented, and thereby particularly affects larger deformation levels. Conversely, the lack of a cross-link results in the onset of intermolecular sliding during deformation and as a result an overall weaker structure. Through a detailed analysis of the distribution of deformation by calculating the molecular strain we show that the location of largest strains does not occur around the covalent bonding region, but is found in regions further away from this location. The insight developed from understanding collagenous materials from a fundamental molecular level upwards could play a role in advancing our understanding of physiological and disease states of connective tissues, and also enable the development of new scaffolding material for applications in regenerative medicine and biologically inspired materials. Keywords

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Section: Resultssupporting

confidence: 78%

Section: Molecular Structurementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen

Uzel

Buehler

2011

Journal of the Mechanical Behavior of Biomedical Materials

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“…Since pioneering experimental works by Fraser, Hulmes, Hess, Orgel, Fratzl and others it is known that virtually all collagen-based tissues are organized into hierarchical structures, where the lowest hierarchical level consists of triple helical collagen molecules (Fig. 1) [2][3][4][5][6][7][8]. Collagen fibrils consist of high-aspect-ratio polypeptides, tropocollagen molecules, with a length of ≈300 nm and a diameter of about 1.5 nm, which are laterally staggered.…”

Section: Introductionmentioning

confidence: 99%

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

Gautieri

Vesentini²,

Redaelli³

et al. 2011

Nano Lett.

596

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.

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“…Therefore we have to consider the definition of the acidity constant (for acetic acid in this example; however, all equations can be generalized for any weak acid and strong base) Furthermore, we have to take into account the definition of the dissociation constant of water (3) Upon addition of NaOH these equilibrium conditions are affected. We need to ensure that the number of charges is conserved ([Na + ] = [NaOH]): (4) Equations (1) - (4) have to be coupled and solved in order to determine the pH before the stoichiometric point is reached as a function of the acid and base concentrations.…”

Section: Evolution Of a Ph Gradient In The Microchannelsmentioning

confidence: 99%

An In Situ Study of Collagen Self-Assembly Processes

et al. 2007

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We present in situ studies on the self-assembly and dynamic evolution of collagen gels from semidilute solutions in a microfluidic device. Collagen fibrils not only reinforce the mechanical properties of bone and tissues, but they also influence cellular motility and morphology. We access the initial steps of the hierarchical self-assembly of collagen fibrils and networks by using hydrodynamic focusing to form oriented fibers. The accurate description of the conditions within the microchannel requires a numerical expression for the pH in the device, as well as a modified mathematical description of the viscosity, which increases nearly 300-fold as collagen fibrils form around neutral pH. Finite element modeling profiles overlay impressively with crossed polarized microscopy images of the birefringent fibrils in the channel. Real-time X-ray microdiffraction measurements in flow indicate an enhanced supramolecular packing having a unit spacing commensurate with that of a pentameric collagen subunits. These results have significant implications for the field of biomedicine, wherein new aligned, cellularly active, and mechanically strengthened materials continue to be in demand. However, this work is also remarkable from a more fundamental, biophysical point of view, since the underlying concepts may be generalized to a large pool of systems.

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The In Situ Supermolecular Structure of Type I Collagen

Cited by 300 publications

References 27 publications

Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen

Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen

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

An In Situ Study of Collagen Self-Assembly Processes

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