Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate

Abstract

Stem cells respond to nanoscale surface features, with changes in cell growth and differentiation mediated by alterations in cell adhesion. The interaction of nanotopographical features with integrin receptors in the cells' focal adhesions alters how the cells adhere to materials surfaces, and defines cell fate through changes in both cell biochemistry and cell morphology. In this Review, we discuss how cell adhesions interact with nanotopography, and we provide insight as to how materials scientists can exploit these interactions to direct stem cell fate and to understand how the behaviour of stem cells in their niche can be controlled. We expect knowledge gained from the study of cell–nanotopography interactions to accelerate the development of next-generation stem cell culture materials and implant interfaces, and to fuel discovery of stem cell therapeutics to support regenerative therapies.

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Figure 1: The nanoscale structure of focal adhesions, and nanoscale connectivity to the cytoskeleton.
Figure 2: Interaction of cells with RGD groups and nanoscale topography.
Figure 3: Nanoscale disorder and adhesion bridging.
Figure 4: Natural and synthetic nanopatterns that offer templates for MSC differentiation and self-renewal.
Figure 5: Cytoskeletal contraction and intracellular tension is important for MSC differentiation.
Figure 6: Image showing marrow-niche architecture and use of paired nanotopographical controls to aid study of MSC growth and differentiation, and to aid understanding of niche regulation.
Figure 7: A model of direct mechanotransduction considering the MSC as a mechanical unit.

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Acknowledgements

M.J.D, N.G. and R.O.C.O. are funded by grants from BBSRC, EPSRC and MRC. We gratefully acknowledge the encouragement and support of M. Riehle, A. Curtis and the late C. Wilkinson. We thank C. Ranson (Glasgow School of Art) for illustrations of the MSC niche and mechanotransduction. We thank R. Fraser and A. Warren (University of Sydney) for interesting discussions on, and images of, fenestrae. Finally, we thank W. Cushley, C. Berry and J. Dalby for critical reading of the manuscript.

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Correspondence to Matthew J. Dalby.

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Dalby, M., Gadegaard, N. & Oreffo, R. Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate. Nature Mater 13, 558–569 (2014). https://doi.org/10.1038/nmat3980

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