PhD opportunity: Collagen

Understanding and exploiting the phenomenal properties of collagen
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.Tropocollagen is unstable at body temperature,driving its formation into supertwisted, right-handed microfibrils with molecules packed in a quasi-hexagonal lattice.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 mechanicaland 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

 

Research Activities
The student will undertake a project in one of the following areas exploring and translating the interesting structure-property relationships in collagen.

  • Understanding health and disease in collagen networks via modelling and advanced imaging;
  • Development of materials to reproduce collagen function for biomedical or industrial applications (collaboration with the Botnar Research Centre, University of Oxford);
  • Understanding the fundamental physical properties of collagen.
  • Exploring and exploiting collagen piezoelectricity.

Students with a physics, materials, mechanical or electrical engineering background are encouraged to apply.

 

Expected outcomes
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.

 

References
1          Shoulders, M. D. & Raines, R. T. Collagen Structure and Stability. Annual Review of Biochemistry78, 929-958 (2009).

2          Leikina, E., Mertts, M. V., Kuznetsova, N. & Leikin, S. Type I collagen is thermally unstable at body temperature. PNAS99, 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. PNAS103, 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 Lett11, 757-766 (2011).

6          Anderson, J. C. & Eriksson, C. Electrical Properties of Wet Collagen. Nature218, 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 Nano3, 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 Mater11, 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 Mater11, 724-733 (2012).

10        Nair, A. K., Gautieri, A., Chang, S.-W. & Buehler, M. J. Molecular mechanics of mineralized collagen fibrils in bone. Nat Commun4, 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 Commun4(2013).

12        Brown, C. P. Advancing musculoskeletal research with nanoscience. Nature Reviews Rheumatology9, 614-623 (2013).