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Theme 2 colloquium: 'Studying the molecular mechanism of collagen mineralization in living and non-living in vitro systems' (Lecture)

Tuesday 12 November 2019Add to my calendar
from 16:00
prof. Nico Sommerdijk (RU/RUMC)

Nico SommerdijkThe mineralized collagen fibril is the basic building block of our bones and as such lies at the basis of the remarkable mechanical properties of bone. Due to its complex organization, its nanoscopic dimensions and hybrid composition, the detailed analysis of the structure of the mineralized collagen fibril has proven difficult. It is an even more challenging task to unravel the mechanism by which collagen is mineralized, as this occurs on the nanometer scale, through a multistep process and in a complex aqueous multicomponent environment. Understanding the process of collagen mineralization is not only will open the way to the development of new treatments for bone defects and mineralization-related diseases, but will also offer new opportunities for the design of new bio-inspired materials. In particular, the ability to build, in vitro, a self-standing unit that can form mineralized collagen under biological control, will have many implications in medicine, pharmaceutical and biomedical engineering.

Previous cryoTEM investigations towards the mechanism of bone formation revealed that the mineralization of calcium phosphate confined within the collagen matrix leads to the formation of apatite platelets which are geometrically and crystallographically oriented along the long axis of the collagen. [1] It was also shown that apatite formation is preceded by disordered precursor phases that transform in to the final crystalline material through a multistep process.[2,3] Now we demonstrate that the ability of collagen to direct the shape and orientation of crystals in not restricted to apatite. Crystals of other minerals formed within confinement of the collagen matrix have similar sizes, shapes and orientations show the generic of character of the template. By a careful investigation of the collagen crystal structure we reveal exiting new details about the mechanism by which collagen directs the mineralization in bone.

More recently we have studied the mineralization of collagen in a “living in vitro” cell culture system by growing human mesenchymal stem cells (hMSC) on a 3D silk scaffold and letting these differentiate into bone forming cells. We monitor the 3D cell culture development using µ-CT, fluorescent microscopy, FIB/SEM and TEM. These hMSCs differentiate into osteoblasts and further into osteocytes and extract collagen fibrils. The collagen fibrils resemble those that are found in natural bones (~20 nm thick). The extracellular matrix is then mineralized by the calcium and phosphate ions that are present in the cell culture medium.  Using Raman and FTIR spectroscopy we characterize the material as carbonated hydroxyapatite and collagen. These results set the stage for the use of our 3D living in vitro system to study the process of collagen mineralization with high resolution and under cryogenic conditions using a combination of electron and fluorescent microscopic techniques.


  • [1] Nudelman, K. Pieterse, A. George, P.H.H. Bomans, H. Friedrich, L. J. Brylka, P.A.J. Hilbers, G. de With N.A.J.M. Sommerdijk, Nature Mater, 9 1004 (2010).
  • [2] Dey, P.H.H. Bomans, F.A. Müller, J. Will, P.M. Frederik, G. de With and N.A.J.M. Sommerdijk, Nature Mater, 9 1010 (2010).
  • [3] J.E.M. Habraken, J. Tao, L.J. Brylka, H. Friedrich, L. Bertinetti, A.S. Schenk, A. Verch, V. Dmitrovic, P.H.H. Bomans, P.M. Frederik, J. Laven, P. van der Schoot, B. Aichmayer, G. de With, J.J. DeYoreo, N.A.J.M. Sommerdijk, Nature Comms 4, 1507 (2013).
dr. Evan Spruijt/ dr. Peter Korevaar