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Nanotopographical Manipulation of Focal Adhesion Formation for Enhanced Differentiation of Human Neural Stem Cells

Authors
 Kisuk Yang  ;  Kyuhwan Jung  ;  Eunkyung Ko  ;  Jin Kim  ;  Kook In Park  ;  Jinseok Kim  ;  Seung-Woo Cho 
Citation
 ACS APPLIED MATERIALS & INTERFACES, Vol.5(21) : 10529-10540, 2013 
Journal Title
 ACS APPLIED MATERIALS & INTERFACES 
ISSN
 1944-8244 
Issue Date
2013
MeSH
Cell Differentiation/drug effects ; Coated Materials, Biocompatible/chemistry ; Coated Materials, Biocompatible/pharmacology* ; Fibronectins/chemistry ; Focal Adhesions/drug effects* ; Humans ; Nanotechnology/methods* ; Neural Stem Cells/cytology* ; Neurodegenerative Diseases/therapy ; Osteoblasts/cytology ; Osteoblasts/drug effects ; Polymers/chemistry ; Polymers/pharmacology
Keywords
differentiation ;  focal adhesion ;  human neural stem cells ;  mechanotransduction ;  nanotopography
Abstract
Manipulating neural stem cell (NSC) fate is of great importance for improving the therapeutic efficacy of NSCs to treat neurodegenerative disorders. Biophysical cues, in addition to biochemical factors, regulate NSC phenotype and function. In this study, we assessed the extent to which surface nanotopography of culture substrates modulates human NSC (hNSC) differentiation. Fibronectin-coated polymer substrates with diverse nanoscale shapes (groove and pillar) and dimensions (ranging from 300 to 1500 nm groove width and pillar gap) were used to investigate the effects of topographical cues on hNSC morphology, alignment, focal adhesion, and differentiation. The majority of nanopatterned substrates induced substantial changes in cellular morphology and alignment along the patterned shapes, leading to alterations in focal adhesion and F-actin reorganization. Certain types of nanopatterned substrates, in particular the ones with small nanostructures (e.g., 300-300 nm groove ridges and 300-300 nm pillar diameter gaps), were found to effectively enhance focal adhesion complex development. Consequently, these substrates enhanced hNSC differentiation toward neurons and astrocytes. Nanotopographical-induced formation of focal adhesions in hNSCs activates integrin-mediated mechanotransduction and intracellular signaling pathways such as MEK-ERK, which may ultimately promote gene expression related to NSC differentiation. This strategy of manipulating matrix surface topography could be applied to develop culture substrates and tissue engineered scaffolds that improve the efficacy of NSC therapeutics.
Full Text
http://pubs.acs.org/doi/abs/10.1021/am402156f
DOI
10.1021/am402156f
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88606
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