Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour

Frith, Jessica E., Mills, Richard J. and Cooper-White, Justin J. (2012) Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour. Journal of Cell Science, 125 2: 317-327. doi:10.1242/jcs.087916

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Author Frith, Jessica E.
Mills, Richard J.
Cooper-White, Justin J.
Title Lateral spacing of adhesion peptides influences human mesenchymal stem cell behaviour
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
Publication date 2012-01-15
Sub-type Article (original research)
DOI 10.1242/jcs.087916
Open Access Status File (Publisher version)
Volume 125
Issue 2
Start page 317
End page 327
Total pages 11
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Collection year 2013
Language eng
Abstract Mesenchymal stem cells (MSCs) have attracted great interest in recent years for tissue engineering and regenerative medicine applications due to their ease of isolation and multipotent differentiation capacity. In the past, MSC research has focussed on the effects of soluble cues, such as growth factors and cytokines; however, there is now increasing interest in understanding how parameters such as substrate modulus, specific extracellular matrix (ECM) components and the ways in which these are presented to the cell can influence MSC properties. Here we use surfaces of self-assembled maleimide-functionalized polystyrene-block-poly(ethylene oxide) copolymers (PS-PEO-Ma) to investigate how the spatial arrangement of cell adhesion ligands affects MSC behaviour. By changing the ratio of PS-PEO-Ma in mixtures of block copolymer and polystyrene homopolymer, we can create surfaces with lateral spacing of the PEO-Ma domains ranging from 34 to 62 nm. Through subsequent binding of cysteine–GRGDS peptides to the maleimide-terminated end of the PEO chains in each of these domains, we are able to present tailored surfaces of controlled lateral spacing of RGD (arginine-glycine-aspartic acid) peptides to MSCs. We demonstrate that adhesion of MSCs to the RGD-functionalized block-copolymer surfaces is through specific attachment to the presented RGD motif and that this is mediated by α5, αV, β1 and β3 integrins. We show that as the lateral spacing of the peptides is increased, the ability of the MSCs to spread is diminished and that the morphology changes from well-spread cells with normal fibroblastic morphology and defined stress-fibres, to less-spread cells with numerous cell protrusions and few stress fibres. In addition, the ability of MSCs to form mature focal adhesions is reduced on substrates with increased lateral spacing. Finally, we investigate differentiation and use qRT-PCR determination of gene expression levels and a quantitative alkaline phosphatase assay to show that MSC osteogenesis is reduced on surfaces with increased lateral spacing while adipogenic differentiation is increased. We show here, for the first time, that the lateral spacing of adhesion peptides affects human MSC (hMSC) properties and might therefore be a useful parameter with which to modify hMSC behaviour in future tissue engineering strategies.
Keyword Mesenchymal stem cell
RGD peptide
Cell morphology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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