Collagen

Collagen (classified into various types) is any of a group of insoluble, fibrous proteins that occur in skin, tendons, vasculature, organs, bones, and cartilage of vertebrate animals.

Quotes

 * Misleading data, false ideas, problems of personal interrelationships occur in much if not all scientific work. Consider, for example, the discovery of the basic structure of collagen, the major protein of tendons, cartilage, and other tissues. The basic fiber of collagen is made of three long chains wound around one another. Its discovery had all the elements that surrounded the discovery of the double helix. The characters are just as colorful and diverse. The facts were just as confused and the false solutions just as misleading. Competion and friendliness also played a part in the story. Yet nobody has written even one book about the race for the triple helix. This is surely because, in a very real sense, collagen is not as important a molecule as DNA. Of course this depends to some extent on what you consider important. Before Alex Rich and I worked (quite by accident, incidentally) on collagen, we tended to be rather patronizing about it. "After all," we said, "there's no collagen in plants." In 1955, after we got interested in the molecule, we found ourselves saying, "Do you realize that one-third of all the protein in your body is collagen?" But however you look at it, DNA is more important than collagen, more central to biology, and more significant for further research. So, as I have said before: It is the molecule that has the glamour, not the scientists.


 * Collagen type I is the most abundant protein in mammals. It confers mechanical stability, strength and toughness to a range of tissues from tendons and ligaments, to skin, cornea, bone and dentin. These tissues have quite different mechanical requirements, some need to be elastic or to store mechanical energy and others need to be stiff and tough. This shows the versatility of collagen as a building material. While in some cases (bone and dentin) the stiffness is increased by the inclusion of mineral, the mechanical properties are, in general, adapted by a modification of the hierarchical structure rather than by a different chemical composition. The basic building block of collagen-rich tissues is the collagen fibril, a fiber with 50 to a few hundred nanometer thickness. These fibrils are then assembled to a variety of more complex structures with very different mechanical properties.


 * Collagen is the primary component of the extracellular matrix in the human body. It has proved challenging to fabricate collagen scaffolds capable of replicating the structure and function of tissues and organs. We present a method to 3D-bioprint collagen using freeform reversible embedding of suspended hydrogels (FRESH) to engineer components of the human heart at various scales, from capillaries to the full organ. Control of pH-driven gelation provides 20-micrometer filament resolution, a porous microstructure that enables rapid cellular infiltration and microvascularization, and mechanical strength for fabrication and perfusion of multiscale vasculature and tri-leaflet valves. We found that FRESH 3D-bioprinted hearts accurately reproduce patient-specific anatomical structure as determined by micro–computed tomography. Cardiac ventricles printed with human cardiomyocytes showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole.


 * The origin of collagen, the dominant structural component of metazoan extracellular matrix, has long been cited as a critical step in the evolution of metazoan multicellularity. While collagens were once thought to be found only in metazoans, scattered reports of collagen domains in Fungi, and more recently in close relatives of metazoans, have called into question whether collagens are truly unique to metazoans. Here, we take advantage of recently sequenced genomes and transcriptomes of diverse holozoans (the clade encompassing metazoans and their close relatives), as well as publicly available proteomes from diverse non-holozoan eukaryotes, to conduct a systematic search for collagen domains across eukaryotic diversity. We find that collagen domains are ubiquitous in choanoflagellates, the sister group of metazoans, and widespread across many other major eukaryotic taxa. Many predicted collagens in non-metazoans are comparable to metazoan collagens in length and proline content. Moreover, most are present in species that also encode putative prolyl 4-hydroxylase domains, suggesting that, like metazoan collagens, they may be stabilized through the hydroxylation of prolines. Fibrillar collagen and collagen IV appear to be unique to metazoans, and we posit that their ability to assemble into superstructures may have contributed to the origin of metazoan multicellularity.
 * Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.