title: Nanotopographical effects on mesenchymal stem cell morphology and phenotype.
abstract: There is a rapidly growing body of literature on the effects of topography and critically, nanotopography on cell adhesion, apoptosis and differentiation. Understanding the effects of nanotopography on cell adhesion and morphology and the consequences of cell shape changes in the nucleus, and consequently, gene expression offers new approaches to the elucidation and potential control of stem cell differentiation. In the current study we have used molecular approaches in combination with immunohistology and transcript analysis to understand the role of nanotopography on mesenchymal stem cell morphology and phenotype. Results demonstrate large changes in cell adhesion, nucleus and lamin morphologies in response to the different nanotopographies. Furthermore, these changes relate to alterations in packing of chromosome territories within the interphase nucleus. This, in turn, leads to changes in transcription factor activity and functional (phenotypical) signalling including cell metabolism. Nanotopography provides a useful, non-invasive tool for studying cellular mechanotransduction, gene and protein expression patterns, through effects on cell morphology. The different nanotopographies examined, result in different morphological changes in the cyto- and nucleo-skeleton. We propose that both indirect (biochemical) and direct (mechanical) signalling are important in these early stages of regulating stem cell fate as a consequence of altered metabolic changes and altered phenotype. The current studies provide new insight on cell-surface interactions and enhance our understanding of the modulation of stem cell differentiation with significant potential application in regenerative medicine.
authors.affiliation: Centre for Cell Engineering, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK.
authors.forename: Penelope
authors.initials: P
authors.lastname: Tsimbouri
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Gadegaard
authors.forename: Karl
authors.initials: K
authors.lastname: Burgess
authors.forename: Kate
authors.initials: K
authors.lastname: White
authors.forename: Paul
authors.initials: P
authors.lastname: Reynolds
authors.forename: Pawel
authors.initials: P
authors.lastname: Herzyk
authors.forename: Richard
authors.initials: R
authors.lastname: Oreffo
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dalby
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure*; D048430:Cell Shape / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000648:ultrastructure*; D010641:Phenotype; D044968:Regenerative Medicine; D015398:Signal Transduction
keywords: FOCAL ADHESIONS; MSC; NANOTOPOGRAPHY; PHENOTYPE