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Fibrillogenesis is the development of fine fibrils normally present in collagen fibers of connective tissue. It is derived from the Greek fibrillo (meaning fibrils, or pertaining to fibrils) and genesis (to create, the process by which something is created).

The assembly of collagen fibrils, fibrillogenesis appears to be a self-assembly process although there is much speculation about the specifics of the mechanism through with the body produces collagen fibrils.[1] In the body, collagen fibrils are composed of several types of collagen as well as macromolecules. Collagen I is the most abundant structural macromolecule within the vertebrate body and also represents the most abundant collagen found within various collagen fibrils[2] There are immense differences in the types of collagen fibrils that exist within the body. For instance, fibrils within the tendon vary in width and are banded into aggregates that form fibril bundles that resist forces of tension within one dimension. Similarly, fibrils that form the translucent corneal stromal matrix form orthogonal sheets and withstand the force of traction in two dimensions. Remarkably, these two structurally different collagen fibrils are speculated to be formed from the same molecules with Collagen I being the primary collagen found within both structures.[2]


There is no concrete evidence or agreement on the exact mechanisms of Fibrillogenesis, however, multiple hypotheses based on primary research put forth various mechanisms to consider. Collagen fibrillogenesis occurs in the plasma membrane during embryonic development. Interestingly, collagen within the body has a denaturation temperature between 32-40 degrees Celsius, the physiological temperature also falls within this range and thereby poses a significant problem.[3] It is therefore a mystery how collagen survives within the tissues in order to yield itself to the formation of collagen fibrils. A postulated solution to the problem of denaturation based on current research, is that newly formed collagen gets stored in vacuoles. The storage vacuoles also contain molecular aggregates that provide the required thermal stability to allow for fibrillogenesis to occur within the body.[3] In the body, fibrillar collagens have over 50 known binding partners.[1] The cell accounts for the variety of binding partners through the localization of the fibrillogenesis process to the plasma membrane in order to maintain control of which molecules bind to each other and further ensure both fibril diversity and assemblies of certain collagen fibrils in different tissues [1] Kader, Hill, and Canty-Larid published a plausible mechanism for the formation of collagen fibrils. Fibronectin a glycoprotein that binds to receptor proteins known as integrins within the cytoskeleton is a key player in the hypothesized method of fibrillogenesis. The interaction between fibronectin and the integrin receptor causes a conformational change in the fibronectin. Additional receptors bind to fibronectin bringing in Collagen I, procollagen I and collagen V. These molecules interact with fibronectin to promote fibril formation on the surface of the cell.[1]


Based on research done using Mice and studies of Ehlers-Danlos Syndrome (EDS), which is characterized by hypermobility of the joints and high levels of skin laxtivity, researcher found that Tenascin-X expression levels correlated with the number of present collagen fibrils. In humans, Tenasin-X is associated with EDS. Through their research, researcher confounded the original hypothesis that tenasin-x interfered with collagen fibrillogenesis and suggest that it acts rather as a regulator of collagen fibrillogenesis. Data suggest tenasin-x is a regulator of collagen fibril spacing. In vitro tests yield evidence that suggest tenasin-x accelerates collagen fibril formation through an additive mechanism when collagen VI is present.[1] In addition to tenasin-x, multiple proteins, glycoconjugates, and small molecules have shown to influence not only the rate of collagen fibrillogenesis, but also the structure of collagen fibrils as well as their size in lab studies.

Medical Significance[edit]

A better understanding of the mechanisms of collagen fibrillogenesis as well as an understanding of the regulators of the process would allow for a better understanding of diseases that affect collagen fibril formation and assembly such as Ehlers-Danlos Syndrome (EDS). On a broader spectrum, an understanding of the processes that lie behind fibrillogenesis would allow for great advancements in the field of regenerative medicine. A greater understanding would lead to a potential future in which organs and tissue damaged through trauma could be regenerated using the basis of collagen fibrillogenesis.


  1. ^ a b c d e Kader, Karl (2008). "Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators". Current Opinion in Cell Biology. 20 (5–24): 495–501. doi:10.1016/ PMC 2577133Freely accessible. PMID 18640274. 
  2. ^ a b Hansen, Uwe; Peter Bruckner (July 2003). "Macromolecular Specificity of Collagen Fibrillogenesis FIBRILS OF COLLAGENS I AND XI CONTAIN A HETEROTYPIC ALLOYED CORE AND A COLLAGEN I SHEATH" (PDF). Journal of Biological Chemistry. 278 (39): 37352–37359. doi:10.1074/jbc.M304325200. PMID 12869566. 
  3. ^ a b Trelstad, Robert; Kimiko Hayashi; Jerome Gross (July 19, 1976). "Collagen fibrillogenesis: Intermediate aggregates and suprafibrillar order". Cell Biology. 73 (11): 4027–4031. Bibcode:1976PNAS...73.4027T. doi:10.1073/pnas.73.11.4027. PMC 431312Freely accessible. PMID 1069288. 

See also[edit]