title: Extending neurites sense the depth of the underlying topography during neuronal differentiation and contact guidance.
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.
authors: 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.
authors: Jie Shi
authors: JS
authors: Chua
authors: Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.
authors: Choon-Peng
authors: CP
authors: Chng
authors: Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore.
authors: Aung Aung Kywe
authors: AA
authors: Moe
authors: 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.
authors: Jason Y
authors: JY
authors: Tann
authors: Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore.
authors: Eyleen L K
authors: EL
authors: Goh
authors: 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.
authors: Keng-Hwee
authors: KH
authors: Chiam
authors: 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.
authors: Evelyn K F
authors: EK
authors: Yim
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D004129:Dimethylpolysiloxanes / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D004129:Dimethylpolysiloxanes
keywords: Modelling; Nanotopography; Neural progenitor cells; Neural tissue engineering; Neuronal differentiation