Skip to main content
SpringerLink
Log in

In Vitro Analysis of the Co-Assembly of Type-I and Type-III Collagen

  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

An important step towards achieving functional diversity of biomimetic surfaces is to better understand the co-assembly of the extracellular matrix components. For this, we study type-I and type-III collagen, the two major collagen types in the extracellular matrix. By using atomic force microscopy, custom image analysis, and kinetic modeling, we study their homotypic and heterotypic assembly. We find that the growth rate and thickness of heterotypic fibrils decrease as the fraction of type-III collagen increases, but the fibril nucleation rate is maximal at an intermediate fraction of type-III. This is because the more hydrophobic type-I collagen nucleates fast and grows in both longitudinal and lateral directions, whereas more hydrophilic type-III limits lateral growth of fibrils, driving more monomers to nucleate additional fibrils. This demonstrates that subtle differences in physico-chemical properties of similar molecules can be used to fine-tune their assembly behavior.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Bierbaum, S., R. Beutner, T. Hanke, D. Scharnweber, U. Hempel, and H. Worch. Modification of Ti6Al4V surfaces using collagen I, III, and fibronectin. I. Biochemical and morphological characteristics of the adsorbed matrix. J. Biomed. Mater. Res. A 67(2):421–430, 2003.

  2. Birk, D. E. Type V collagen: heterotypic type I/V collagen interactions in the regulation of fibril assembly. Micron 32(3):223–237, 2001.

    Article  Google Scholar 

  3. Birk, D. E. and R. Mayne. Localization of collagen types I, III and V during tendon development. changes in collagen types I and III are correlated with changes in fibril diameter. Eur. J. Cell Biol. 72(4):352–361, 1997.

    Google Scholar 

  4. Birk, D. E. and F. H. Silver. Collagen fibrillogenesis in vitro: comparison of types I, II, and III. Arch. Biochem. Biophys. 235(1):178–185, 1984.

    Article  Google Scholar 

  5. Bozec, L., G. van der Heijden, and M. Horton. Collagen fibrils: nanoscale ropes. Biophys. J. 92(1):70–75, 2007.

    Article  Google Scholar 

  6. Bruckner, P. Suprastructures of extracellular matrices: paradigms of functions controlled by aggregates rather than molecules. Cell Tissue Res. 339(1):7–18, 2010.

    Article  Google Scholar 

  7. Chanut-Delalande, H., A. Fichard, S. Bernocco, R. Garrone, D. J. S. Hulmes, and F. Ruggiero. Control of heterotypic fibril formation by collagen V is determined by chain stoichiometry. J. Biol. Chem. 276(26):24352–24359, 2001.

    Article  Google Scholar 

  8. Cisneros, D. A., J. Friedrichs, A. Taubenberger, C. M. Franz, and D. J. Muller. Creating ultrathin nanoscopic collagen matrices for biological and biotechnological applications. Small 3(6):956–963, 2007.

    Article  Google Scholar 

  9. Cisneros, D. A., C. Hung, C. M. Franz, and D. J. Muller. Observing growth steps of collagen self-assembly by time-lapse high-resolution atomic force microscopy. J. Struct. Biol. 154(3):232–245, 2006.

    Article  Google Scholar 

  10. Dong, M., S. Xu, M. H. Bünger, H. Birkedal, and F. Besenbacher. Temporal assembly of collagen type II studied by atomic force microscopy. Adv. Eng. Mater. 9(12):1129–1133, 2007.

    Article  Google Scholar 

  11. Elliott, J. T., A. Tona, J. T. Woodward, P. L. Jones, and A. L. Plant. Thin films of collagen affect smooth muscle cell morphology. Langmuir 19(5):1506–1514, 2003.

    Article  Google Scholar 

  12. Engel, J. and M. Chiquet. An overview of extracellular matrix structure and function. In: The Extracellular Matrix: An Overview, edited by R. P. Mecham. Heidelberg: Springer, 2011, pp. 1–39.

    Chapter  Google Scholar 

  13. Fang, M., E. L. Goldstein, E. K. Matich, B. G. Orr, and M. M. Banaszak Holl. Type I collagen self-assembly: the roles of substrate and concentration. Langmuir 29(7):2330–2338, 2013.

    Article  Google Scholar 

  14. Fleischmajer, R., J. S. Perlish, R. E. Burgeson, F. Shaikh-Bahai, and R. Timpl. Type I and type III collagen interactions during fibrillogenesis. Ann. N.Y. Acad. Sci. 580(1):161–175, 1990.

    Article  Google Scholar 

  15. Fratzl, P. Collagen: Structure and Mechanics. New York: Springer, 2008.

  16. Friedrichs, J., A. Taubenberger, C. M. Franz, and D. J. Muller. Cellular remodelling of individual collagen fibrils visualized by time-lapse AFM. J. Mol. Biol. 372(3):594–607, 2007.

    Article  Google Scholar 

  17. Gale, M., M. Pollanen, P. Markiewicz, and M. Goh. Sequential assembly of collagen revealed by atomic force microscopy. Biophys. J. 68(5):2124–2128, 1995.

    Article  Google Scholar 

  18. Gay, S. and E. J. Miller. Collagen in the Physiology and Pathology of Connective Tissue. Stuttgart: Fischer, 1978.

  19. Helseth, D. L. and A. Veis. Collagen self-assembly in vitro. Differentiating specific telopeptide-dependent interactions using selective enzyme modification and the addition of free amino telopeptide. J. Biol. Chem. 256(14):7118–7128, 1981.

    Google Scholar 

  20. Heydarkhan-Hagvall, S., K. Schenke-Layland, A. P. Dhanasopon, F. Rofail, H. Smith, B. M. Wu, R. Shemin, R. E. Beygui, and W. R. MacLellan. Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering. Biomaterials 29(19):2907–2914, 2008.

    Article  Google Scholar 

  21. Hwang, W. and E. Eryilmaz. Kinetic signature of fractal-like filament networks formed by orientational linear epitaxy. Phys. Rev. Lett. 113(2):025502, 2014.

    Article  Google Scholar 

  22. Javid, N., S. Roy, M. Zelzer, Z. Yang, J. Sefcik, and R. V. Ulijn. Cooperative self-assembly of peptide gelators and proteins. Biomacromolecules 14(12):4368–4376, 2013.

    Article  Google Scholar 

  23. Jiang, F., H. Hörber, J. Howard, and D. J. Müller. Assembly of collagen into microribbons: effects of pH and electrolytes. J. Struct. Biol. 148(3):268–278, 2004.

    Article  Google Scholar 

  24. Kadler, K. E., C. Baldock, J. Bella, and R. P. Boot-Handford. Collagens at a glance. J. Cell Sci. 120(12):1955–1958, 2007.

    Article  Google Scholar 

  25. Kadler, K. E., Y. Hojima, and D. J. Prockop. Assembly of collagen fibrils de novo by cleavage of the type I pC-collagen with procollagen C-proteinase. Assay of critical concentration demonstrates that collagen self-assembly is a classical example of an entropy-driven process. J. Biol. Chem. 262(32):15696–15701, 1987.

    Google Scholar 

  26. Keene, D. R., L. Y. Sakai, H. P. Bächinger, and R. E. Burgeson. Type III collagen can be present on banded collagen fibrils regardless of fibril diameter. J. Cell Biol. 105(5):2393–2402, 1987.

    Article  Google Scholar 

  27. Kuwahara, Y. Comparison of the surface structure of the tetrahedral sheets of muscovite and phlogopite by AFM. Phys.Chem. Miner. 28(1):1–8, 2001.

    Article  Google Scholar 

  28. Kuznetsova, N. and S. Leikin. Does the triple helical domain of type I collagen encode molecular recognition and fiber assembly while telopeptides serve as catalytic domains? Effect of proteolytic cleavage on fibrillogenesis and on collagen–collagen interaction in fibers. J. Biol. Chem. 274(51):36083–36088, 1999.

    Article  Google Scholar 

  29. Lee, C. H., A. Singla, and Y. Lee. Biomedical applications of collagen. Int. J. Pharm. 221(1):1–22, 2001.

    Article  Google Scholar 

  30. Leow, W. W. and W. Hwang. Epitaxially guided assembly of collagen layers on mica surfaces. Langmuir 27(17):10907–10913, 2011.

    Article  Google Scholar 

  31. Liu, S. H., R.-S. Yang, R. Al-Shaikh, and J. M. Lane. Collagen in tendon, ligament, and bone healing: a current review. Clin. Orthop. Relat. Res. 318:265–278, 1995.

    Google Scholar 

  32. Liu, X., H. Wu, M. Byrne, S. Krane, and R. Jaenisch. Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc. Natl Acad. Sci. U.S.A. 94(5):1852–1856, 1997.

    Article  Google Scholar 

  33. Loo, R. W. and M. C. Goh. Potassium ion mediated collagen microfibril assembly on mica. Langmuir 24(23):13276–13278, 2008.

    Article  Google Scholar 

  34. Lutolf, M. P. and J. A. Hubbell. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat. Biotechnol. 23(1):47–55, 2005.

    Article  Google Scholar 

  35. Monroe, M. R., Y. Li, S. B. Ajinkya, L. B. Gower, and E. P. Douglas. Directed collagen patterning on gold-coated silicon substrates via micro-contact printing. Mater. Sci. Eng. C 29(8):2365–2369, 2009.

    Article  Google Scholar 

  36. Mouw, J. K., G. Ou, and V. M. Weaver. Extracellular matrix assembly: a multiscale deconstruction. Nat. Rev. Mol. Cell Biol. 15(12):771–785, 2014.

    Article  Google Scholar 

  37. Narayanan, B., G. H. Gilmer, J. Tao, J. J. De Yoreo, and C. V. Ciobanu. Self-assembly of collagen on flat surfaces: the interplay of collagen–collagen and collagen–substrate interactions. Langmuir 30(5):1343–1350, 2014.

    Article  Google Scholar 

  38. Notbohm, H., S. Mosler, P. K. Müller, and J. Brinckmann. In vitro formation and aggregation of heterotypic collagen I and III fibrils. Int. J. Biol. Macromol. 15(5):299–304, 1993.

    Article  Google Scholar 

  39. Ostendorf, F., C. Schmitz, S. Hirth, A. Kuhnle, J. J. Kolodziej, and M. Reichling. How flat is an air-cleaved mica surface? Nanotechnology 19:305705–305711, 2008.

    Article  Google Scholar 

  40. Papi, M., V. Palmieri, G. Maulucci, G. Arcovito, E. Greco, G. Quintiliani, M. Fraziano, and M. De Spirito. Controlled self assembly of collagen nanoparticle. J. Nanopart. Res. 13(11):6141–6147, 2011.

    Article  Google Scholar 

  41. Peacock, J. D., Y. Lu, M. Koch, K. E. Kadler, and J. Lincoln. Temporal and spatial expression of collagens during murine atrioventricular heart valve development and maintenance. Dev. Dyn. 237(10):3051–3058, 2008.

    Article  Google Scholar 

  42. Piechocka, I. K., A. S. G. van Oosten, R. G. M. Breuls, and G. H. Koenderink. Rheology of heterotypic collagen networks. Biomacromolecules 12(7):2797–2805, 2011.

    Article  Google Scholar 

  43. Ravikumar, K. M. and W. Hwang. Role of hydration force in the self-assembly of collagens and amyloid steric zipper filaments. J. Am. Chem. Soc. 133(30):11766–11773, 2011.

    Article  Google Scholar 

  44. Ricard-Blum, S. The collagen family. Cold Spring Harb. Perspect. Biol. 3(1):a004978, 2011.

    Article  Google Scholar 

  45. Romanic, A. M., E. Adachi, K. E. Kadler, Y. Hojima, and D. J. Prockop. Copolymerization of pNcollagen III and collagen I. pNcollagen III decreases the rate of incorporation of collagen I into fibrils, the amount of collagen I incorporated, and the diameter of the fibrils formed. J. Biol. Chem. 266(19):12703–12709, 1991.

    Google Scholar 

  46. Salhi, B., F. Vaurette, B. Grandidier, D. Stiévenard, O. Melnyk, Y. Coffinier, and R. Boukherroub. The collagen assisted self-assembly of silicon nanowires. Nanotechnology 20(23):235601, 2009.

    Article  Google Scholar 

  47. Silver, F. H. A two step model for lateral growth of collagen fibrils. Collagen Relat. Res. 3(3):167–179, 1983.

    Article  Google Scholar 

  48. Silver, F. H., I. Horvath, and D. J. Foran. Mechanical implications of the domain structure of fiber-forming collagens: comparison of the molecular and fibrillar flexibilities of the α1-chains found in types I–III collagen. J. Theor. Biol. 216(2):243–254, 2002.

    Article  Google Scholar 

  49. Speranza, M. L., G. Valentini, and A. Calligaro. Influence of fibronectin on the fibrillogenesis of type I and type III collagen. Collagen Relat. Res. 7(2):115–123, 1987.

    Article  Google Scholar 

  50. Spiess, K. and T. M. T. Zorn. Collagen types I, III, and V constitute the thick collagen fibrils of the mouse decidua. Microsc. Res. Tech. 70(1):18–25, 2007.

    Article  Google Scholar 

  51. Stuart, K. and A. Panitch. Characterization of gels composed of blends of collagen I, collagen III, and chondroitin sulfate. Biomacromolecules 10(1):25–31, 2009.

    Article  Google Scholar 

  52. Sun, M., A. Stetco, and Merschrod S, E. F. Surface-templated formation of protein microfibril arrays. Langmuir 24(10):5418–5421, 2008.

  53. Teodoro. W. R., S. S. Witzel, A. P. P. Velosa, M. Shimokomaki, P. A. Abrahamsohn, and T. M. T. Zorn. Increase of interstitial collagen in the mouse endometrium during decidualization. Connect. Tissue Res.. 44(2):96–103, 2003.

    Article  Google Scholar 

  54. Volk, S. W., Y. Wang, E. A. Mauldin, K. W. Liechty, and S. L. Adams. Diminished type III collagen promotes myofibroblast differentiation and increases scar deposition in cutaneous wound healing. Cells Tissues Organs 194(1):25–37, 2011.

    Article  Google Scholar 

  55. Wess, T. J. Collagen fibril form and function. Adv. Protein Chem. 70:341–374, 2005.

    Article  Google Scholar 

  56. Wu, J. J., M. A. Weis, L. S. Kim, and D. R. Eyre. Type III collagen, a fibril network modifier in articular cartilage. J. Biol. Chem. 285(24):18537–18544, 2010.

    Google Scholar 

  57. Zhu, B., Q. Lu, J. Yin, J. Hu, and Z. Wang. Alignment of osteoblast-like cells and cell-produced collagen matrix induced by nanogrooves. Tissue Eng. 11(5-6):825–834, 2005.

    Article  Google Scholar 

Download references

Acknowledgments

We acknowledge using the Texas A & M Materials Characterization Facility for part of the experiments. Esma Eryilmaz was supported by the Turkish Ministry of Education fellowship.

Conflict of Interest

Esma Eryilmaz, Winfried Teizer, and Wonmuk Hwang declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

No human studies were carried out by the authors of this article. No animal studies were carried out by the authors of this article.

Author information

Authors and Affiliations

  1. Department of Physics and Astronomy, Texas A&M University, College Station, TX, 77843, USA

    Esma Eryilmaz

  2. Department of Biotechnology, College of Science, Selcuk University, Konya, 42003, Turkey

    Esma Eryilmaz

  3. Departments of Physics and Astronomy and Materials Science & Engineering, Texas A&M University, College Station, TX, 77843, USA

    Winfried Teizer

  4. WPI Advanced Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Sendai, 980-8577, Japan

    Winfried Teizer

  5. Department of Biomedical Engineering and Materials Science & Engineering, Texas A&M University, College Station, TX, 77843, USA

    Wonmuk Hwang

  6. School of Computational Sciences, Korea Institute for Advanced Study, Seoul, 02455, Korea

    Wonmuk Hwang

Authors
  1. Esma Eryilmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Winfried Teizer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wonmuk Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wonmuk Hwang.

Additional information

Communicated by Associate Editor Mian Long oversaw the review of this article.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 521 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eryilmaz, E., Teizer, W. & Hwang, W. In Vitro Analysis of the Co-Assembly of Type-I and Type-III Collagen. Cel. Mol. Bioeng. 10, 41–53 (2017). https://doi.org/10.1007/s12195-016-0466-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-016-0466-3

Keywords

Search

Navigation