type-VI Collagen Research Articles

Cartilage-derived cells display heterogeneous pericellular matrix synthesis in agarose microgels

The pericellular matrix (PCM) surrounding chondrocytes is essential for articular cartilage tissue engineering. As the current isolation methods to obtain chondrocytes with their PCM (chondrons) result in a heterogeneous mixture of chondrocytes and chondrons, regenerating the PCM using a tissue engineering approach could prove beneficial. In this study, we aimed to discern the behavior of articular chondrocytes (ACs) in regenerating the PCM in such an approach and whether this would also be true for articular cartilage-derived progenitor cells (ACPCs), as an alternative cell source. Bovine ACs and ACPCs were encapsulated in agarose microgels using droplet-based microfluidics. ACs were stimulated with TGF-β1 and dexamethasone and ACPCs were sequentially stimulated with BMP-9 followed by TGF-β1 and dexamethasone. After 0, 3, 5, and 10 days of culture, PCM components, type-VI collagen and perlecan, and ECM component, type-II collagen, were assessed using flow cytometry and fluorescence microscopy. Both ACs and ACPCs synthesized the PCM before the ECM. It was seen for the first time that synthesis of type-VI collagen always preceded perlecan. While the PCM synthesized by ACs resembled native chondrons after only 5 days of culture, ACPCs often made less well-structured PCMs. Both cell types showed variations between individual cells and donors. On one hand, this was more prominent in ACPCs, but also a subset of ACPCs showed superior PCM and ECM regeneration, suggesting that isolating these cells may potentially improve cartilage repair strategies.

Involvement of non‑triple helical typeVI collagenα1 chain, NTHα1(VI), in the proliferation of cancer cells.

It has been reported that a polypeptide encoded by collagen typeVI alpha1 chain (COL6A1), one of the threeα chains of typeVI collagen, is strongly associated with the migration and invasion of highly metastatic human pancreatic cancer BxPC‑M8 cells and excessive proliferation of LNCaPcells. We previously reported that non‑triple helical typeVI collagenα1 chain, NTHα1(VI), a non‑triple helical polypeptide encoded by COL6A1, is not derived from typeVI collagen and exists in cancer cell‑conditioned media. Therefore, NTHα1(VI) may be involved in cancer cell migration, invasion, and proliferation. The active entity that promotes cellular behaviors in cancer remains unclear. Thus, we predicted that NTHα1(VI) has cancer‑promoting activity, such as the ability to induce cell proliferation. This study was conducted to examine whether NTHα1(VI) and/or its derived peptides are involved in cancer cell proliferation. Highly metastatic human pancreatic S2‑VP10cells were used to explore the potential of COL6A1 knockdown in reducing cell proliferation. Moreover, S2‑VP10 conditioned medium was assessed after molecular size‑fractionation to determine whether the inhibitory effect of COL6A1 knockdown could be rescued by the medium. We showed that S2‑VP10‑conditioned medium contained COL6A1 polypeptide, but not COL6A2, suggesting that COL6A1 in the conditioned medium of S2‑VP10cells reflects the presence of NTHα1(VI). COL6A1 knockdown repressed S2‑VP10cell proliferation and this repression was rescued using the conditioned medium of S2‑VP10cells. The fraction of conditioned medium containing peptides smaller than 10kDa rescued the inhibitory effect; however, the fraction containing polypeptides larger than 10kDa, including NTHα1(VI), did not show rescue activity, indicating that NTHα1(VI) fragmentation is necessary for enhanced cancer cell proliferation. In conclusion, fragmentation of NTHα1(VI) into peptides <10kDa is required for its cancer cell proliferation‑promoting activity.

ILC2 Lung-Homing in Cystic Fibrosis Patients: Functional Involvement of CCR6 and Impact on Respiratory Failure.

Cystic fibrosis patients suffer from a progressive, often fatal lung disease, which is based on a complex interplay between chronic infections, locally accumulating immune cells and pulmonary tissue remodeling. Although group-2 innate lymphoid cells (ILC2s) act as crucial initiators of lung inflammation, our understanding of their involvement in the pathogenesis of cystic fibrosis remains incomplete. Here we report a marked decrease of circulating CCR6+ ILC2s in the blood of cystic fibrosis patients, which significantly correlated with high disease severity and advanced pulmonary failure, strongly implicating increased ILC2 homing from the peripheral blood to the chronically inflamed lung tissue in cystic fibrosis patients. On a functional level, the CCR6 ligand CCL20 was identified as potent promoter of lung-directed ILC2 migration upon inflammatory conditions in vitro and in vivo using a new humanized mouse model with light-sheet fluorescence microscopic visualization of lung-accumulated human ILC2s. In the lung, blood-derived human ILC2s were able to augment local eosinophil and neutrophil accumulation and induced a marked upregulation of pulmonary type-VI collagen expression. Studies in primary human lung fibroblasts additionally revealed ILC2-derived IL-4 and IL-13 as important mediators of this type-VI collagen-inducing effect. Taken together, the here acquired results suggest that pathologically increased CCL20 levels in cystic fibrosis airways induce CCR6-mediated lung homing of circulating human ILC2s. Subsequent ILC2 activation then triggers local production of type-VI collagen and might thereby drive extracellular matrix remodeling potentially influencing pulmonary tissue destruction in cystic fibrosis patients. Thus, modulating the lung homing capacity of circulating ILC2s and their local effector functions opens new therapeutic avenues for cystic fibrosis treatment.

Chondrogenic Differentiation of Human Adipose-Derived Stem Cells in PLGA (Poly(Lactic-Co-Glycolic Acid) Scaffold

Human adipose tissue contain a population of pluripotent stem cells capable of differentiating along multiple mesenchymal cell lineages. The goal of this study was to examine the chondrogenic potential of adipose-derived stem (ADS) cells. ADS cells were isolated from human subcutaneous adipose tissue obtained by lipectomy and liposuction, and were expanded and grown in vitro with or without chondrogenic medium in micromass culture condition and 3D culture condition in PLGA(poly(lactic-co-glycolic acid)) scaffold. Human ADS cells of micromass culture condition and 3D culture condition in PLGA scaffolds, were differentiated with chondrogenic medium consisted of transforming growth factor-β1, insulin-transferrin-selenium, dexamethasone and ascorbate-2-phosphate. ADS cells abundantly synthesized cartilage matrix molecules including collagen type II, VI and link protein. ADS cells under high-density micromass culture condition with chondrogenic medium formed well defined nodules within 48 hours of induction. On the 3rd week after chondrogenic differentiation of ADS cells under the micromass culture condition and 3D culture condition of PLGA scaffold, mRNA of type II collagen, type VI collagen and link protein were expressed by reverse transcription polymerase chain reaction (RT-PCR). On the 3weeks, content of glycosaminoglycan in cells treated with chondrogenic medium was greater than that with non chondrogenic medium(control).On the 3rd week culture under the chondrogenic medium, hematoxylin &amp; eosin (H &amp; E) staining, alcian blue staining and type II collagen immunohistochemistry analysis confirmed the chondrogenic differentiation in micromass and 3D cultured specimen. These findings document the ability of ADS cells to produce characteristic cartilage matrix molecules, and provide the possibility of cartilage regeneration for cartilage substitution.

Zonal changes in the three-dimensional morphology of the chondron under compression: The relationship among cellular, pericellular, and extracellular deformation in articular cartilage

The pericellular matrix (PCM) is a narrow region of tissue that completely surrounds chondrocytes in articular cartilage. Previous theoretical models of the “chondron” (the PCM with enclosed cells) suggest that the structure and properties of the PCM may significantly influence the mechanical environment of the chondrocyte. The objective of this study was to quantify changes in the three-dimensional (3D) morphology of the chondron in situ at different magnitudes of compression applied to the cartilage extracellular matrix. Fluorescence immunolabeling for type-VI collagen was used to identify the boundaries of the cell and PCM, and confocal microscopy was used to form 3D images of chondrons from superficial, middle, and deep zone cartilage in explants compressed to 0%, 10%, 30%, and 50% surface-to-surface strain. Lagrangian tissue strain, determined locally using texture correlation, was highly inhomogeneous and revealed depth-dependent compressive stiffness and Poisson's ratio of the extracellular matrix. Compression significantly decreased cell and chondron height and volume, depending on the zone and magnitude of compression. In the superficial zone, cellular-level strains were always lower than tissue-level strains. In the middle and deep zones, however, tissue strains below 25% were amplified at the cellular level, while tissue strains above 25% were decreased at the cellular level. These findings are consistent with previous theoretical models of the chondron, suggesting that the PCM can serve as either a protective layer for the chondrocyte or a transducer that amplifies strain, such that cellular-level strains are more homogenous throughout the tissue depth despite large inhomogeneities in local ECM strains.

Cell Deformation and Micromechanical Environment in the Intervertebral Disc

The purpose of this research was to explore the in situ anatomic and mechanical environment of disc cells. Laser scanning confocal microscopy was used to characterize three-dimensional morphology of intervertebral disc cells, micromechanical deformation and interaction with extracellular matrix, and functional intercellular communication. Bovine coccygeal discs were used for both the anatomic and micromechanical investigations. Anulus fibrosus cells had a complex morphology with sinuous processes woven into the extracellular matrix, particularly in the outer aspect of the anulus where they were also interconnected via functional gap junctions. They were also found in an extensive pericellular matrix of type-VI collagen, joining as many as ten cells into linear cell arrays that could be extracted from the matrix as functional units. Mechanically, collagen fibril sliding was demonstrated to govern cell mechanics and strain transfer in the anulus fibrosus during loading activities. Lamellar cells were largely protected from direct tensile strains in the matrix, with minimal intercellular strains. However, intercellular strains between lamellar cells in adjacent arrays were large, illustrating shearing between linear cell arrays. Appreciable shear was observed across the lamellar cell bodies as well as to the cellular processes woven into the matrix. These findings demonstrated the morphologic and micromechanical complexity of anulus fibrosus cells. The knowledge of the in situ environment of disc cells will provide a base to investigate the mechanical implications of disc degeneration on the cellular environment and to better understand how mechanical and genetic risk factors can impact the cells that are essential to maintaining the intervertebral disc.

Substrate-Dependent Morphology of Supramolecular Assemblies: Fibrillin and Type-VI Collagen Microfibrils

Substrate hydrophobicity/hydrophilicity has previously been shown to affect the morphology and biological function of isolated proteins. We have employed atomic force microscopy to investigate substrate dependent morphologies of two biochemically distinct native supramolecular assemblies: fibrillin and type-VI collagen microfibrils. These morphologically heterogeneous microfibrillar systems are found in many vertebrate tissues where they perform structural and cell-signaling roles. Fibrillin microfibrils adsorbed to a hydrophilic mica substrate adopted a diffuse morphology. Fibrillin microfibrils adsorbed to mica coated with poly- l-lysine or to borosilicate glass substrates had a more compact morphology and a directional asymmetry to the bead, which was not present on mica alone. Intermediate morphologies were observed along a substrate gradient. The classical double-beaded appearance of type-VI collagen microfibrils was evident on mica coated with poly- l-lysine and on glass. On hydrophilic mica, morphology was severely disrupted and there was a major conformational reorganization along the whole collagen microfibril repeat. These observations of substrate dependent conformation have important implications for the interpretation of data from in vitro protein interaction assays and cellular signaling studies. Furthermore, conformational changes may be induced by local charge environments in vivo, revealing or hiding binding sites.

Tenascin: a sensitive and specific diagnostic marker of minimal collagenous colitis.

Collagenous colitis is a rare cause of chronic watery diarrhea. In this condition, endoscopic findings are usually normal. Currently, the diagnosis relies on the histological presence of thick subepithelial bands of collagen deposits and an inflammatory infiltrate within the mucosa. However, these subepithelial bands may be developed only focally and may be too subtle to allow a definitive diagnosis upon routine hematoxylin and eosin (HE) and van Gieson's stainings. Recently, we and others were able to show a prominent staining of tenascin and type-VI collagen in the subepithelial band-like structures. In this study, we tested the diagnostic value of tenascin staining and type-VI collagen immunolocalization for the identification of collagenous colitis and compared it with conventional histology and histochemical detection of collagens. The analysis was based on 434 biopsy specimens of collagenous colitis, other forms of colitis, and normal mucosa. We were able to show that the immunohistochemical detection of increased amounts of tenascin, selectively in the subepithelial zone, is a specific test for collagenous colitis, with a sensitivity superior to conventional histological and histochemical detection, especially in minimal collagenous colitis (P<0.001). Of note, tenascin staining also allows the diagnosis of collagenous colitis in biopsies obtained only from the rectum and sigmoid colon, thus avoiding the need for colonoscopic investigations. Tenascin immunostaining is a simple and safe tool to complement conventional histological diagnostics in clinically and histopathologically unclear cases of diarrhea.

Increased content of type-VI collagen epitopes in human osteoarthritic cartilage: quantitation by inhibition ELISA.

Type-VI collagen is an integral part of the extracellular cartilage matrix. However, the exact amounts of type-VI collagen in normal and osteoarthritic human cartilage still are not known. In this study, we describe an inhibition enzyme-linked immunosorbent assay that was developed to quantitate type-VI collagen epitopes found in guanidinium chloride extracts from normal and osteoarthritic human cartilage. In 31 cartilage samples from various localizations of healthy adult human knees, type-VI collagen epitopes accounted for approximately 0.40% of the total collagen content. Interestingly, type-VI collagen epitopes increased about 4-fold in osteoarthritic cartilage. A statistically significant increase of type-VI collagen epitopes was found during early stages of the disease, with only a superficial roughening of the cartilage surface and a loss of proteoglycans. Thus, these findings indicate that type-VI collagen is a minor component of normal human articular cartilage and that the amount of type-VI collagen epitopes increases significantly during early stages of osteoarthritis.

Spatial and temporal changes of type VI collagen expression during mouse development.

The expression of type VI collagen has been studied in mouse tissues. By Northern blotting, the mRNA for the alpha 1 (VI) chain was detectable in whole embryos at 10.5 days postcoitum and steeply increased afterward. The messenger levels were high at birth, but decreased rapidly in the following days, reaching low levels in adult animals. In 2-month-old mice, lung, skin, adrenal gland, heart, skeletal muscle and tail and fat were among the most active producers of alpha 1 (VI) mRNA. In situ hybridization first identified mRNA for alpha 1 (VI) collagen in mesenchymal cells of 10.5-day embryos in various locations, including serosae, branchial arches, large blood vessels and the cephalic mesenchyme. Staining increased at later stages of development and most connective tissues were positive at 16.5 days and later. Strongly staining tissues were joints, intervertebral disks, perichondrium, periostium, dermis, skeletal muscle and heart valves, whereas cartilage and bone were very poorly labelled. Epithelia and the central nervous system were completely negative. In several organs, notably lung, salivary glands and the digestive tract, staining was concentrated underneath epithelia. This staining pattern was different from that for collagen type I, which was evenly distributed in the subepithelial mesenchyme. The pattern of distribution of the protein, revealed by immunocytochemistry, was coincident with that of the alpha 1 (VI) mRNA. In addition, the results confirmed that type VI collagen is preferentially deposited in the pericellular environment. This was particularly evident in skeletal muscle. The data show that type VI collagen is mainly produced by mesenchymal cells and suggest a role for the protein in delineating the boundary of distinct domains in connective tissue.

The Macromolecular Structure of Type-VI Collagen. Formation and Stability of Filaments

Type-VI collagen microfilaments were directly isolated from human amnion without using strong denaturing reagents. The microfilaments were characterized by electron microscopy, SDS/PAGE and immunoprecipitation. There was no evidence of other components bound to the isolated filaments and no covalent bonds between adjacent tetramers. The association between tetramers was further analyzed by studying the affinity between globular domains and the helix of type-VI collagen. Solid-phase-binding assays and conventional column chromatography showed that the globular domains have a high affinity for each other and for the helices of type-VI collagen, indicating that filaments may be assembled and stabilized in the absence of additional components. Hyaluronan did not stabilize the filaments nor facilitate the assembly of tetramers into filaments. The interaction between domains was also studied after modifying the sugar moieties of type-VI collagen globular domains and monomeric triple-helical domains. The oligosaccharides are involved in helix-helix interactions but not in interactions of the globular domains with each other or with the triple helix.

The Macromolecular Structure of Type-VI Collagen. Formation and Stability of Filaments

Type-VI collagen microfilaments were directly isolated from human amnion without using strong denaturing reagents. The microfilaments were characterized by electron microscopy, SDS/PAGE and immunoprecipitation. There was no evidence of other components bound to the isolated filaments and no covalent bonds between adjacent tetramers. The association between tetramers was further analyzed by studying the affinity between globular domains and the helix of type-VI collagen. Solid-phase-binding assays and conventional column chromatography showed that the globular domains have a high affinity for each other and for the helices of type-VI collagen, indicating that filaments may be assembled and stabilized in the absence of additional components. Hyaluronan did not stabilize the filaments nor facilitate the assembly of tetramers into filaments. The interaction between domains was also studied after modifying the sugar moieties of type-VI collagen globular domains and monomeric triple-helical domains. The oligosaccharides are involved in helix-helix interactions but not in interactions of the globular domains with each other or with the triple helix.

Type-VI collagen as a major component in the interstitial matrix of cutaneous mechanoreceptors.

The presence or absence of type-VI collagen in mechanoreceptors in the lips and palate of the mouse and gerbil was assessed histochemically. When fresh palatine mucosae and the lips of mice were incubated in 20 mM ATP solution, numerous fibrous long spacing fibers with a periodicity of 100 nm appeared in the interlamellar spaces of Meissner's corpuscles, simple lamellated corpuscles, and the peripheral connective tissue of Ruffini's nerve endings, irrespective of age. In addition, when the palatine mucosae of mice and gerbils were stained immunohistochemically with anti-type-VI collagen, an intensely positive reaction was constantly observed in Meissner's corpuscles. Furthermore, a less intense immunoreaction to anti-type-VI collagen was recognized in the inner core of simple lamellated corpuscles and Ruffini-like formations in the labial mucosae. From these results, we conclude that type-VI collagen is a major constituent of the interstitial connective tissue of cutaneous mechanoreceptors.

Spinal deformity in Ehlers-Danlos syndrome. Five patients treated by spinal fusion

Five patients with classical Ehlers-Danlos syndrome developed severe spinal deformities. Two were shown to have type-VI collagen abnormalities. Three had a double structural scoliosis of the thoracic and lumbar regions, one had a single thoracic scoliosis and one had a thoracic kyphosis. The curves first developed before the age of four years, and were not controlled by bracing. Major corrective surgery with posterior fusion was performed at a mean age of 11 years 8 months. Excessive blood loss could be controlled and although wound haematoma and dehiscence were common, they did not provide major problems. The spinal fusions healed satisfactorily.

Ultrastructural immunolocalization of type‐VI collagen and chondroitin sulphate in ligament

Immunological methods were used to determine the identity of the major components comprising a network of electron-dense seams (described by the authors in a previous work) within the extracellular matrix of medial collateral ligament (MCL) from humans and rabbits. Tissue obtained from MCL midsubstance was subjected to pre-embedding labelling with colloidal gold at the electron microscopic level with monoclonal antibodies (MAbs) against type-VI collagen and chondroitin sulphate (CS), before and after digestion with chondroitinase ABC and testicular hyaluronidase. Tissue labelled with anti-type-VI MAbs showed gold conjugates attached to the microfilamentous component of the seams both before and after enzyme digestion, which confirmed the identity of the beaded microfilaments as type-VI collagen. Treatment of the tissue with anti-CS MAbs resulted in labelling of undigested tissue only. In these treatments, gold particles were found attached to granules that were interspersed throughout the network of type-VI microfilaments. Both the granules and gold labels were absent from the network following enzyme digestion. Thin nonbeaded microfilaments that did not label with anti-type-VI MAbs also were present within the seams. The loss of these nonbeaded microfilaments following enzyme digestion suggested that they might represent strands of hyaluronan. The codistribution and sequestering of type-VI collagen and CS within discrete seams or channels suggests that these regions of the MCL midsubstance may contain higher concentrations of water than the surrounding dense fibrillar matrix.

Stable expression of chicken type‐VI collagen α1, α2 and α3 cDNAs in murine NIH/3T3 cells

As a component of an extensive network of microfibrils interwoven with large collagen fibers and in close contact with cell surfaces, type VI collagen plays an important role in cell-matrix interactions. To investigate the behaviour of chicken type VI collagen chains in heterologous host cells as a means to understanding the pattern of assembly of this collagen, we transfected murine NIH/3T3 cells with cDNAs encoding chicken alpha 1(VI), alpha 2(VI) and alpha 3(VI) chains. Cell lines that constitutively expressed the individual chains were analyzed by metabolic labeling and immunoprecipitation with specific antibodies. No self-association was observed for either alpha 1(VI) or alpha 2(VI) chains which were secreted as monomeric polypeptides. Furthermore, neither the chicken alpha 1(VI) nor alpha 2(VI) chains associated with the endogenous murine chains to form chimeric chicken/murine heterotrimers. In contrast, chimeric chicken/murine heterotrimers were detected in cell lines transfected with chicken alpha 3(VI) cDNA. These chimeric forms appeared to be properly aligned since their triple helices were stable to pepsin digestion. In addition, the chimeric heterotrimers coassembled and gave rise to disulfide-linked type VI collagen molecules.

Type-VI collagen in the human iris and ciliary body

The distribution of type-VI collagen in the human iris and ciliary body was investigated by means of immunohistochemical techniques and compared with that of type-IV collagen, fibronectin and laminin. As has been described for other tissues, type-VI collagen surrounds type-I and -III collagen fibers. The aggregated form of type-VI collagen (the "long-spacing" or "curly" collagen), which has already been described in the trabecular meshwork and sclera, was also observed at the ciliary muscle tips surrounding the anterior elastic tendons of this muscle. In addition, staining for type-VI collagen was seen directly adjacent to the basement membranes of the ciliary muscle cells, the iris muscles, the uveal vascular endothelia and nerves, but not adjacent to the epithelial basement membranes. The staining did not form a discrete line like the immunoreaction for type-IV collagen, but bundles of marked fibrils extended into the surrounding connective tissue. We assume that type-VI collagen similar to type-VII collagen forms part of an anchoring system for these tissues. As type-VII collagen has been described only in connection with epithelial basement membranes, both type-VI and type-VII collagens may represent anchoring fibrils, however for different tissue components.

Characterization of tissue from the bone-polymethylmethacrylate interface in a rat experimental model. Demonstration of collagen-degrading activity and bone-resorbing potential.

In previous studies, we described a layer of tissue that formed around methylmethacrylate cement that had been implanted into the posterior cervical spine of dogs. We are now reporting on a rat model in which we induced, in the interface between the bone of the posterior elements of the dorsal spine and methylmethacrylate, the formation of a layer of tissue that was morphologically similar to the tissue that had been produced in the dogs. As in the dogs, we noted macrophages and giant cells and we demonstrated that the interface tissue synthesized several basement-membrane components (type-IV collagen, laminin, and fibronectin). In addition, we demonstrated the synthesis of an additional extracellular-matrix protein--type-VI collagen. We also showed that extracts of organ cultures of tissue from the rat model degraded type-I collagen into three-quarter and one-quarter-length fragments. Such enzymatic activity is characterized of mammalian collagenase, an enzyme that is known to play a critical role in the resorption of bone.

An immunohistochemical study of human endometrial extracellular matrix during the menstrual cycle and first trimester of pregnancy.

Changes in the organisation and composition of extracellular matrix in human endometrium during the menstrual cycle and early pregnancy have been assessed by immunofluorescence. Amongst interstitial components, type-III and type V-collagens and fibronectin are present in endometrial stroma throughout the menstrual cycle as well as in first trimester decidua. Type V-collagen epitopes are masked early in the cycle, but become accessible in first trimester decidua. Type VI-collagen is abundant in endometrium in the proliferative phase, but is progressively lost in the secretory phase and decidua, in which it is retained only in blood vessel walls. Vitronectin is present in some blood vessels in decidua. Decidualising stromal cells also produce basement membrane components (type IV-collagen, laminin, heparan sulphate proteoglycan and a glycoprotein family recognised by monoclonal antibody G71) and these become organised into a pericellular aura.

Aggregation of platelets by collagen: polar active sites of insoluble human collagen.

ARTICLESAggregation of platelets by collagen: polar active sites of insoluble human collagenGD Wilner, HL Nossel, and TL ProcupezGD Wilner, HL Nossel, and TL ProcupezPublished Online:01 Apr 1971https://doi.org/10.1152/ajplegacy.1971.220.4.1074MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByIn vitro capacity of different grades of chitosan derivatives to induce platelet adhesion and aggregationInternational Journal of Biological Macromolecules, Vol. 52Efficacy of Different Hemostatic Devices for Severe Liver Bleeding: A Randomized Controlled Animal Study23 September 2010 | Surgical Innovation, Vol. 17, No. 4Self-aggregation of fibrillar collagens I and II involves lysine side chainsMicron, Vol. 37, No. 7A novel collagen-based composite offers effective hemostasis for multiple surgical indications: Results of a randomized controlled trialSurgery, Vol. 129, No. 4Control of Bone Bleeding at the Sternum and Iliac Crest Donor Sites Using a Collagen-Based Composite Combined With Autologous Plasma: Results of a Randomized Controlled TrialOrthopedics, Vol. 24, No. 2Collagen - platelet interaction: Inhibition by a monoclonal antibody which binds a 90,000 dalton platelet glycoproteinThrombosis Research, Vol. 53, No. 2The Platelet Reactivity of Collagen Type VICollagen and Related Research, Vol. 5, No. 6The platelet reactivity of the of α2(I-chain of type I collagen: Platelet aggregation induce by polymers of the molecule [α2(I)]I3Thrombosis Research, Vol. 39, No. 4Hymie Nossel (11 July 1930 – 8 October 1983)Thrombosis Research, Vol. 34, No. 1Isolation and purification of collagen alpha 1(I) receptor from human platelet membrane.Journal of Biological Chemistry, Vol. 257, No. 13On the role of the major platelet membrane glycoproteins in platelet adhesion to collagenThrombosis Research, Vol. 22, No. 4Platelet adhesion onto artificial red blood cellsJournal of Biomedical Materials Research, Vol. 14, No. 3Characteristics of the major platelet membrane site used in binding to collagenThrombosis Research, Vol. 15, No. 5-6Platelet adhesion to type III collagen: Involvement of a sequence of nine aminoacids from α1(III)CB4 peptideThrombosis Research, Vol. 16, No. 1-2Collagen–Platelet InteractionCollagen-induced platelet aggregation and release. I effects of side-chain modifications and role of arginyl residuesBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 544, No. 3Collagen-induced platelet aggregation: Native collagen quaternary structure is not an essential structural requirementThrombosis Research, Vol. 13, No. 5Adhesion of platelets to collagen. The nature of the binding site from competitive inhibition studiesThrombosis Research, Vol. 12, No. 3Inhibition and enhancement of platelet aggregation by collagen derivativesJournal of Biomedical Materials Research, Vol. 11, No. 3Binding of chick skin collagen alpha 1 chain by isolated membranes from human platelets.Journal of Biological Chemistry, Vol. 251, No. 20An electrostatic model for collagen fibrils. The interaction of reconstituted collagen with Ca++, Na+, and Cl?Biopolymers, Vol. 15, No. 8Fluid-Dynamic Boundary Conditions for Thrombotic Processes in High Shear Environments in vivoREFERENCESInteraction of a chick skin collagen fragment (alpha1-CB5) with human platelets. Biochemical studies during the aggregation and release reaction.Journal of Biological Chemistry, Vol. 250, No. 17Biomedical applications of polymeric materials and their interactions with blood components: a critical review of current developmentsPolymer, Vol. 16, No. 6Microcirculatory Disturbances Induced by Generalized Intravascular CoagulationTHROMBOSISPLATELET ADHESION*16 December 2006 | Annals of the New York Academy of Sciences, Vol. 201, No. 1 More from this issue > Volume 220Issue 4April 1971Pages 1074-1079 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.220.4.1074PubMed5551133History Published online 1 April 1971 Published in print 1 April 1971 Metrics