- Professor Andrew Carr, University of Oxford
- Associate Professor Eamonn Gaffney, University of Oxford
Collagen is the most abundant protein in the human body and, as one of its principal building blocks, plays a dominant role in the function of many tissues. As such, the structure-property-function relationships in collagen are central to understanding health and disease, and developing materials-based strategies for regenerative medicine. A better understanding of these relationships further provides a biomimetic target for high-performance, multifunctional fibre-based materials in applications outside of biomedicine.
The defining feature of collagen is an elegant structural motif in which three parallel polypeptide strands coil with a one-residue stagger to form a right-handed triple helix, known as tropocollagen.1 Tropocollagen is unstable at body temperature,2 driving its formation into supertwisted, right-handed microfibrils with molecules packed in a quasi-hexagonal lattice.3 This leads to a spiral-like structure within the mature collagen fibril, with interdigitated microfibrils forming a networked, nanoscale rope.3,4
The complex hierarchical structure within a collagen fibril provides interesting mechanical5 and electrical6,7 properties, and the basis for interactions with other tissue components. This allows collagen to modulate tissue structure8,9 and therefore function. Through organisation and interactions on the nanometre to micrometre scales, collagen can work effectively in a wide variety of tissue configurations to provide exceptional mechanical performance, tuned to specialised applications.10-12
1 Shoulders, M. D. & Raines, R. T. Collagen Structure and Stability. Annual Review of Biochemistry 78, 929-958 (2009).
2 Leikina, E., Mertts, M. V., Kuznetsova, N. & Leikin, S. Type I collagen is thermally unstable at body temperature. PNAS 99, 1314-1318 (2002).
3 Orgel, J. P. R. O., Irving, T. C., Miller, A. & Wess, T. J. Microfibrillar structure of type I collagen in situ. PNAS 103, 9001-9005 (2006).
4 Bozec, L., van der Heijden, G. & Horton, M. Collagen Fibrils: Nanoscale Ropes. Biophys. J. 92, 70-75 (2007).
5 Gautieri, A., Vesentini, S., Redaelli, A. & Buehler, M. J. Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up. Nano Lett 11, 757-766 (2011).
6 Anderson, J. C. & Eriksson, C. Electrical Properties of Wet Collagen. Nature 218, 166-168 (1968).
7 Minary-Jolandan, M. & Yu, M.-F. Uncovering Nanoscale Electromechanical Heterogeneity in the Subfibrillar Structure of Collagen Fibrils Responsible for the Piezoelectricity of Bone. ACS Nano 3, 1859-1863 (2009).
8 Trappmann, B., Gautrot, J. E., Connelly, J. T., Strange, D. G. T., Li, Y., Oyen, M. L., Cohen Stuart, M. A., Boehm, H., Li, B., Vogel, V., Spatz, J. P., Watt, F. M. & Huck, W. T. S. Extracellular-matrix tethering regulates stem-cell fate. Nat Mater 11, 642-649 (2012).
9 Wang, Y., Azaïs, T., Robin, M., Vallée, A., Catania, C., Legriel, P., Pehau-Arnaudet, G., Babonneau, F., Giraud-Guille, M.-M. & Nassif, N. The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite. Nat Mater 11, 724-733 (2012).
10 Nair, A. K., Gautieri, A., Chang, S.-W. & Buehler, M. J. Molecular mechanics of mineralized collagen fibrils in bone. Nat Commun 4, 1724 (2013).
11 Zimmermann, E. A., Gludovatz, B., Schaible, E., Dave, N. K. N., Yang, W., Meyers, M. A. & Ritchie, R. O. Mechanical adaptability of the Bouligand-type structure in natural dermal armour. Nat Commun 4 (2013).
12 Brown, C. P. Advancing musculoskeletal research with nanoscience. Nature Reviews Rheumatology 9, 614-623 (2013).
A range of projects are available to explore and exploit the interesting structure-property relationships in collagen. Specific projects are in network mechanics, biomaterial development, piezoelectricity and energy harvesting, diagnostics, regenerative medicine and the physics of disease. Many of these projects involve collaborations with the Botnar Research Centre and Mathematical Institute at the University of Oxford.
Potential outcomes from this work are wide-ranging, and will of course depend on the specific project. The student should discuss expected outcomes with Prof. Brown.
Skills and experience
Students with a physics, materials, mechanical or electrical engineering background are encouraged to apply.
You may be able to apply for a research scholarship in our annual scholarship round.
Contact the supervisor for more information.