title: The role of microtopography in cellular mechanotransduction.
abstract: Mechanotransduction is crucial for cellular processes including cell survival, growth and differentiation. Topographically patterned surfaces offer an invaluable non-invasive means of investigating the cell response to such cues, and greater understanding of mechanotransduction at the cell-material interface has the potential to advance development of tailored topographical substrates and new generation implantable devices. This study focuses on the effects of topographical modulation of cell morphology on chromosomal positioning and gene regulation, using a microgrooved substrate as a non-invasive mechanostimulus. Intra-nuclear reorganisation of the nuclear lamina was noted, and the lamina was required for chromosomal repositioning. It appears that larger chromosomes could be predisposed to such repositioning. Microarrays and a high sensitivity proteomic approach (saturation DiGE) were utilised to identify transcripts and proteins that were subject to mechanoregulated changes in abundance, including mediators of chromatin remodelling and DNA synthesis linked to the changes in nucleolar morphology and the nucleoskeleton.
authors.affiliation: Centre for Cell Engineering, Institute of Molecular, Cell & Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK. laura.mcnamara@glasgow.ac.uk
authors.forename: Laura E
authors.initials: LE
authors.lastname: McNamara
authors.forename: Richard
authors.initials: R
authors.lastname: Burchmore
authors.forename: Mathis O
authors.initials: MO
authors.lastname: Riehle
authors.forename: Pawel
authors.initials: P
authors.lastname: Herzyk
authors.forename: Manus J P
authors.initials: MJ
authors.lastname: Biggs
authors.forename: Chris D W
authors.initials: CD
authors.lastname: Wilkinson
authors.forename: Adam S G
authors.initials: AS
authors.lastname: Curtis
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dalby
mesh_terms: D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism; D045584:Chromosome Positioning / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D034882:Lamins / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D018613:Microscopy, Confocal; D040901:Proteomics; D011791:Quartz / Q000737:chemistry* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects; D059467:Transcriptome / Q000235:genetics
chemical_list: D034882:Lamins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011791:Quartz