Changing ligand number and type within nanocylindrical domains through kinetically constrained self-assembly-impacts of ligand 'redundancy' on human mesenchymal stem cell adhesion and morphology

Li, Haiqing and Cooper-White, Justin J. (2014) Changing ligand number and type within nanocylindrical domains through kinetically constrained self-assembly-impacts of ligand 'redundancy' on human mesenchymal stem cell adhesion and morphology. Biomaterials Science, 2 11: 1693-1705. doi:10.1039/c4bm00109e


Author Li, Haiqing
Cooper-White, Justin J.
Title Changing ligand number and type within nanocylindrical domains through kinetically constrained self-assembly-impacts of ligand 'redundancy' on human mesenchymal stem cell adhesion and morphology
Journal name Biomaterials Science   Check publisher's open access policy
ISSN 2047-4849
2047-4830
Publication date 2014-11-01
Year available 2014
Sub-type Article (original research)
DOI 10.1039/c4bm00109e
Open Access Status Not Open Access
Volume 2
Issue 11
Start page 1693
End page 1705
Total pages 13
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Collection year 2015
Language eng
Formatted abstract
In this paper, we firstly describe a facile method by which sequential attachment of different adhesion peptides to a nanotopographical, self-assembled block copolymer cell culture surface is made possible through orthogonal click chemistry. Functionalization of polystyrene-b-polyethylene oxide block copolymers (PS-PEO) with azide (PS-PEO-N3) and aminooxy (PS-PEO-ONH2) moieties permitted the use of orthogonal click chemistry protocols to sequentially add desired bioactive moieties. Thereafter, we show that co-self-assembly of non-functionalised PS-PEO with different amounts of these functionalized PS-PEOs produces polymer films having well-defined, hexagonally arrayed PEO nanocylinder domains, of near constant diameter ([similar]17 nm diameter) and lateral spacing ([similar]35 nm). The invariant diameters and lateral spacing of the nanodomains with changes in the amounts of PS-PEO-N3 and PS-PEO-ONH2 confirmed our ability to tune the number density of these functional groups locally within each PEO nanodomain. Stepwise conjugation of alkyne-terminated IKVAV or aldehyde-terminated RGD to the azide and aminooxy decorated nanodomains produced a series of substrates with increasing local number density of grafted adhesion peptides in each nanodomain. We then systematically investigated the impacts of ligand affinity and availability (leading to differing levels of redundancy) on cell integrin binding and adhesion behaviours. We show that with increasing numbers of single peptides (IKVAV or RGD) or with changes in the ratio of IKVAV and RGD peptides within each of the [similar]17 nm nanodomains of these films, there was significant changes in the number of hMSCs adhered and substantial modulation of cell morphology, cytoskeletal actin stress fibres and focal adhesion maturation. We observed that increases in the ratio of RGD to IKVAV peptides within the constrained surface nanodomains greatly enhanced hMSC adhesion, and effectively modulated hMSC morphology, cytoskeletal actin structures and focal adhesion number and maturity between the two extremes noted for the single peptides. The results presented suggest that these self assembled block copolymer substrates regulate hMSC adhesion and morphology through modulation of ligand affinity and ligand redundancy, and hence the effectiveness of integrin binding and mechanotransduction signalling. These novel 2D polymer substrates offer encoded and defined cues for cell adhesion at length scales previously unrealised and the results of this investigation expose a new parameter set by which the surfaces of biomaterials may be tailored for stem cell culture, selection and fate.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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