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Annual Review of Biochemistry 2009Collagen is the most abundant protein in animals. This fibrous, structural protein comprises a right-handed bundle of three parallel, left-handed polyproline II-type... (Review)
Review
Collagen is the most abundant protein in animals. This fibrous, structural protein comprises a right-handed bundle of three parallel, left-handed polyproline II-type helices. Much progress has been made in elucidating the structure of collagen triple helices and the physicochemical basis for their stability. New evidence demonstrates that stereoelectronic effects and preorganization play a key role in that stability. The fibrillar structure of type I collagen-the prototypical collagen fibril-has been revealed in detail. Artificial collagen fibrils that display some properties of natural collagen fibrils are now accessible using chemical synthesis and self-assembly. A rapidly emerging understanding of the mechanical and structural properties of native collagen fibrils will guide further development of artificial collagenous materials for biomedicine and nanotechnology.
Topics: Animals; Collagen; Humans; Models, Molecular; Protein Multimerization; Protein Stability; Protein Structure, Secondary
PubMed: 19344236
DOI: 10.1146/annurev.biochem.77.032207.120833 -
Matrix Biology : Journal of the... 2015Most abundant in the extracellular matrix are collagens, joined by elastin that confers elastic recoil to the lung, aorta, and skin. These fibrils are highly resistant... (Review)
Review
Most abundant in the extracellular matrix are collagens, joined by elastin that confers elastic recoil to the lung, aorta, and skin. These fibrils are highly resistant to proteolysis but can succumb to a minority of the matrix metalloproteinases (MMPs). Considerable inroads to understanding how such MMPs move to the susceptible sites in collagen and then unwind the triple helix of collagen monomers have been gained. The essential role in unwinding of the hemopexin-like domain of interstitial collagenases or the collagen binding domain of gelatinases is highlighted. Elastolysis is also facilitated by the collagen binding domain in the cases of MMP-2 and MMP-9, and remote exosites of the catalytic domain in the case of MMP-12.
Topics: Binding Sites; Collagen; Elastin; Humans; Matrix Metalloproteinases; Models, Molecular; Protein Binding; Protein Structure, Secondary; Proteolysis; Substrate Specificity
PubMed: 25599938
DOI: 10.1016/j.matbio.2015.01.005 -
Biophysical Journal Jul 2016Type I collagen is the predominant collagen in mature tendons and ligaments, where it gives them their load-bearing mechanical properties. Fibrils of type I collagen are...
Type I collagen is the predominant collagen in mature tendons and ligaments, where it gives them their load-bearing mechanical properties. Fibrils of type I collagen are formed by the packing of polypeptide triple helices. Higher-order structures like fibril bundles and fibers are assembled from fibrils in the presence of other collagenous molecules and noncollagenous molecules. Curiously, however, experiments show that fibrils/fibril bundles are less resistant to axial stress compared to their constituent triple helices-the Young's moduli of fibrils/fibril bundles are an order-of-magnitude smaller than the Young's moduli of triple helices. Given the sensitivity of the Young's moduli of triple helices to solvation environment, a plausible explanation is that the packing of triple helices into fibrils perhaps reduces the Young's modulus of an individual triple helix, which results in fibrils having smaller Young's moduli. We find, however, from molecular dynamics and accelerated conformational sampling simulations that the Young's modulus of the buried core of the fibril is of the same order as that of a triple helix in aqueous phase. These simulations, therefore, suggest that the lower Young's moduli of fibrils/fibril bundles cannot be attributed to the specific packing of triple helices in the fibril core. It is not the fibril core that yields initially to axial stress. Rather, it must be the portion of the fibril exposed to the solvent and/or the fibril-fibril interface that bears the initial strain. Overall, this work provides estimates of Young's moduli and persistence lengths at two levels of collagen's structural assembly, which are necessary to quantitatively investigate the response of various biological factors on collagen mechanics, including congenital mutations, posttranslational modifications and ligand binding, and also engineer new collagen-based materials.
Topics: Biomechanical Phenomena; Collagen Type I; Elastic Modulus; Mechanical Phenomena; Molecular Dynamics Simulation; Nanotechnology; Protein Structure, Secondary
PubMed: 27410733
DOI: 10.1016/j.bpj.2016.05.038 -
International Journal of Molecular... Jan 2021Hydroxyapatite (HA) reinforced collagen fibrils serve as the basic building blocks of natural bone and dentin. Mineralization of collagen fibrils play an essential role... (Review)
Review
Hydroxyapatite (HA) reinforced collagen fibrils serve as the basic building blocks of natural bone and dentin. Mineralization of collagen fibrils play an essential role in ensuring the structural and mechanical functionalities of hard tissues such as bone and dentin. Biomineralization of collagen can be divided into intrafibrillar and extrafibrillar mineralization in terms of HA distribution relative to collagen fibrils. Intrafibrillar mineralization is termed when HA minerals are incorporated within the gap zone of collagen fibrils, while extrafibrillar mineralization refers to the minerals that are formed on the surface of collagen fibrils. However, the mechanisms resulting in these two types of mineralization still remain debatable. In this review, the evolution of both classical and non-classical biomineralization theories is summarized. Different intrafibrillar mineralization mechanisms, including polymer induced liquid precursor (PILP), capillary action, electrostatic attraction, size exclusion, Gibbs-Donnan equilibrium, and interfacial energy guided theories, are discussed. Exemplary strategies to induce biomimetic intrafibrillar mineralization using non-collagenous proteins (NCPs), polymer analogs, small molecules, and fluidic shear stress are discussed, and recent applications of mineralized collagen fibers for bone regeneration and dentin repair are included. Finally, conclusions are drawn on these proposed mechanisms, and the future trend of collagen-based materials for bone regeneration and tooth repair is speculated.
Topics: Biomimetics; Biomineralization; Bone Regeneration; Bone and Bones; Collagen; Dentin; Durapatite; Extracellular Matrix; Humans; Polymers; Tissue Engineering; Wound Healing; X-Ray Diffraction
PubMed: 33477897
DOI: 10.3390/ijms22020944 -
International Journal of Biological... Sep 2022Type I collagen is a ubiquitous structural protein in animal tissues. It is normally present in a hydrated form. However, collagen is very dependent on associated water...
Type I collagen is a ubiquitous structural protein in animal tissues. It is normally present in a hydrated form. However, collagen is very dependent on associated water for its mechanical properties. In skin, where type I collagen is dominant, there is a longstanding concern that the skin and therefore collagen may partially dry out and result in structural degradation. Here we show that dehydration of type I collagen fibrils, using 2-propanol, results in a two-stage dehydration process. Initially, the fibrils do not change length, i.e. the D-period remains constant, but shrinkage occurs within the fibrils by an increase in the gap region and a decrease in the overlap region within a D-band and a shortening of the helical turn distance and fibril diameter. Only with further dehydration does the length of the collagen fibril decrease (a decrease in D-period). This mechanism explains why collagen materials are resistant to gross structural change in the early stages of dehydration and shows why they may then suffer from sudden external shrinkage with further dehydration.
Topics: Animals; Collagen; Collagen Type I; Dehydration; Extracellular Matrix; Skin
PubMed: 35793742
DOI: 10.1016/j.ijbiomac.2022.06.180 -
Acta Biomaterialia Jun 2023Collagen fibrils are the fundamental structural elements in vertebrate animals and compose a structural framework that provides mechanical support to load-bearing... (Review)
Review
Collagen fibrils are the fundamental structural elements in vertebrate animals and compose a structural framework that provides mechanical support to load-bearing tissues. Understanding how these fibrils initially form and mechanically function has been the focus of a myriad of detailed investigations over the last few decades. From these studies a great amount of knowledge has been acquired as well as a number of new questions to consider. In this review, we examine the current state of our knowledge of the mechanical properties of extant fibrils. We emphasize on the mechanical response and related deformation of collagen fibrils upon tension, which is the predominant load imposed in most collagen-rich tissues. We also illuminate the gaps in knowledge originating from the intriguing results that the field is still trying to interpret. STATEMENT OF SIGNIFICANCE: Collagen is the result of millions of years of biological evolution and is a unique family of proteins, the majority of which provide mechanical support to biological tissues. Cells produce collagen molecules that self-assemble into larger structures, known as collagen fibrils. As simple as they appear under an optical microscope, collagen fibrils display a complex ultrastructural architecture tuned to the external forces that are imposed upon them. Even more complex is the way collagen fibrils deform under loading, and the nature of the mechanisms that drive their formation in the first place. Here, we present a cogent synthesis of the state-of-knowledge of collagen fibril mechanics. We focus on the information we have from in vitro experiments on individual, isolated from tissues, collagen fibrils and the knowledge available from in silico tests.
Topics: Animals; Biomechanical Phenomena; Collagen; Extracellular Matrix; Weight-Bearing; Microscopy
PubMed: 36509398
DOI: 10.1016/j.actbio.2022.12.008 -
The Biochemical Journal May 1996Collagen is most abundant in animal tissues as very long fibrils with a characteristic axial periodic structure. The fibrils provide the major biomechanical scaffold for... (Review)
Review
Collagen is most abundant in animal tissues as very long fibrils with a characteristic axial periodic structure. The fibrils provide the major biomechanical scaffold for cell attachment and anchorage of macromolecules, allowing the shape and form of tissues to be defined and maintained. How the fibrils are formed from their monomeric precursors is the primary concern of this review. Collagen fibril formation is basically a self-assembly process (i.e. one which is to a large extent determined by the intrinsic properties of the collagen molecules themselves) but it is also sensitive to cell-mediated regulation, particularly in young or healing tissues. Recent attention has been focused on "early fibrils' or "fibril segments' of approximately 10 microns in length which appear to be intermediates in the formation of mature fibrils that can grow to be hundreds of micrometers in length. Data from several laboratories indicate that these early fibrils can be unipolar (with all molecules pointing in the same direction) or bipolar (in which the orientation of collagen molecules reverses at a single location along the fibril). The occurrence of such early fibrils has major implications for tissue morphogenesis and repair. In this article we review the current understanding of the origin of unipolar and bipolar fibrils, and how mature fibrils are assembled from early fibrils. We include preliminary evidence from invertebrates which suggests that the principles for bipolar fibril assembly were established at least 500 million years ago.
Topics: Animals; Cattle; Chick Embryo; Collagen; Microscopy, Electron; Models, Structural; Morphogenesis; Skin; Tendons
PubMed: 8645190
DOI: 10.1042/bj3160001 -
Genes Jul 2022The fibrillar collagen family is comprised of the quantitatively major types I, II and III collagens and the quantitatively minor types V and XI. These form heterotypic... (Review)
Review
The fibrillar collagen family is comprised of the quantitatively major types I, II and III collagens and the quantitatively minor types V and XI. These form heterotypic collagen fibrils (composed of more than a single collagen type) where the minor collagens have a regulatory role in controlling fibril formation and diameter. The structural pre-requisites for normal collagen biosynthesis and fibrillogenesis result in many places where this process can be disrupted, and consequently a wide variety of phenotypes result when pathogenic changes occur in these fibrillar collagen genes. Another contributing factor is alternative splicing, both naturally occurring and as the result of pathogenic DNA alterations. This article will discuss how these factors should be taken into account when assessing DNA sequencing results from a patient.
Topics: Collagen; Extracellular Matrix; Fibrillar Collagens
PubMed: 35885981
DOI: 10.3390/genes13071199 -
The International Journal of... Aug 2014Collagen XII, largest member of the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical α-chains encoded by the... (Review)
Review
Collagen XII, largest member of the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical α-chains encoded by the COL12A1 gene. The molecule consists of three threadlike N-terminal noncollagenous NC3 domains, joined by disulfide bonds and a short interrupted collagen triple helix toward the C-terminus. Splice variants differ considerably in size and properties: "small" collagen XIIB (220 kDa subunit) is similar to collagen XIV, whereas collagen XIIA (350 kDa) has a much larger NC3 domain carrying glycosaminoglycan chains. Collagen XII binds to collagen I-containing fibrils via its collagenous domain, whereas its large noncollagenous arms interact with other matrix proteins such as tenascin-X. In dense connective tissues and bone, collagen XII is thought to regulate organization and mechanical properties of collagen fibril bundles. Accordingly, recent findings show that collagen XII mutations cause Ehlers-Danlos/myopathy overlap syndrome associated with skeletal abnormalities and muscle weakness in mice and humans.
Topics: Animals; Autoantigens; Collagen Type XII; Contracture; Ehlers-Danlos Syndrome; Fibril-Associated Collagens; Humans; Mice; Muscle Development; Muscles; Muscular Dystrophies; Non-Fibrillar Collagens; Osteogenesis; Collagen Type XVII
PubMed: 24801612
DOI: 10.1016/j.biocel.2014.04.020 -
Biomaterials Aug 2023Although the extracellular matrix (ECM) plays essential roles in heart tissue engineering, the optimal ECM components for heart tissue organization have not previously...
Although the extracellular matrix (ECM) plays essential roles in heart tissue engineering, the optimal ECM components for heart tissue organization have not previously been elucidated. Here, we focused on the main ECM component, fibrillar collagen, and analyzed the effects of collagens on heart tissue engineering, by comparing the use of porcine heart-derived collagen and other organ-derived collagens in generating engineered heart tissue (EHT). We demonstrate that heart-derived collagen induces better contraction and relaxation of human induced pluripotent stem cell-derived EHT (hiPSC-EHT) and that hiPSC-EHT with heart-derived collagen exhibit more mature profiles than those with collagens from other organs. Further, we found that collagen fibril formation and gel stiffness influence the contraction, relaxation, and maturation of hiPSC-EHT, suggesting the importance of collagen types III and type V, which are relatively abundant in the heart. Thus, we demonstrate the effectiveness of organ-specific collagens in tissue engineering and drug discovery.
Topics: Animals; Swine; Humans; Tissue Engineering; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Collagen; Extracellular Matrix
PubMed: 37285642
DOI: 10.1016/j.biomaterials.2023.122174