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Biomaterials. 2014 Sep;35(27):7750-61. doi: 10.1016/j.biomaterials.2014.06.008. Epub 2014 Jun 19.

Extending neurites sense the depth of the underlying topography during neuronal differentiation and contact guidance.

Author information

1
Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore; Mechanobiology Institute Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore.
2
Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.
3
Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore.
4
Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore; Department of Biomedical Engineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117575, Singapore.
5
Mechanobiology Institute Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore; Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore. Electronic address: chiamkh@bii.a-star.edu.sg.
6
Mechanobiology Institute Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore; Department of Biomedical Engineering, National University of Singapore, EA-03-12, 9 Engineering Drive 1, Singapore 117575, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228, Singapore. Electronic address: eyim@nus.edu.sg.

Abstract

The topography of the extracellular microenvironment influences cell morphology, provides conduct guidance and directs cell differentiation. Aspect ratio and dimension of topography have been shown to affect cell behaviours, but the ability and mechanism of depth-sensing is not clearly understood. We showed that murine neural progenitor cells (mNPCs) can sense the depth of the micro-gratings. Neurite elongation, alignment and neuronal differentiation were observed to increase with grating depth. We proposed a mechanism for depth-sensing by growing neurites: filopodial adhesion in the growth cones favour elongation but the bending rigidity of the neurite cytoskeleton resists it. Thus, perpendicular extension on deeper grooves is unfavourable as neurites need to bend over a larger angle. A quantitative model was developed and its prediction of neurite growth on gratings fit well with the experimental data. The results indicated that mNPC fate can be directed by appropriately designed patterned surfaces.

KEYWORDS:

Modelling; Nanotopography; Neural progenitor cells; Neural tissue engineering; Neuronal differentiation

[Indexed for MEDLINE]

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