Journal of Cellular Biochemistry 102:1234–1244 (2007) Nanomechanotransduction and Interphase Nuclear Organization Influence on Genomic Control Matthew J. Dalby, 1 * Nikolaj Gadegaard, 2 Pawel Herzyk, 3 Duncan Sutherland, 4 Hossein Agheli, 4 Chris D.W. Wilkinson, 2 and Adam S.G. Curtis 1 1 Centre for Cell Engineering, Joseph Black Building, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK 2 Centre for Cell Engineering, Rankine Building, Department of Electronics and Electrical Engineering, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK 3 Sir Henry Wellcome Functional Genomics Facility, Joseph Black Building, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK 4 iNANO Interdisciplinary Research Center, University of Aarhus, Aarhus 8000, Denmark Abstract The ability of cells to alter their genomic regulation in response to mechanical conditioning or through changes in morphology and the organization of the interphase nuclei are key questions in cell biology. Here, two nanotopographies have been used as a model surfaces to change cell morphology in order to investigate spatial genomic changes within the nuclei of fibroblasts. Initially, centromeres for chromosome pairs were labeled and the average distance on different substrates calculated. Further to this, Affymetrix whole genome GeneChips 1 were used to rank genomic changes in response to topography and plot the whereabouts on the chromosomes these changes were occurring. It was seen that as cell spreading was changed, so were the positions along the chromosomes that gene regulations were being observed. We hypothesize that as changes in cell and thus nuclear morphology occur, that this may alter the probability of transcription through opening or closing areas of the chromosomes to transcription factors. J. Cell. Biochem. 102: 1234 – 1244, 2007. ß 2007 Wiley-Liss, Inc. Key words: mechanotransduction; microarray; nanobiotechnology; Interphase Nuclear Organization There is increasing evidence that cells can act as mechanosensitive units responding to the mechanical stimulation of the extracellular matrix though focal adhesions and changes in cytoskeletal organization. Mechanotransduc- tion can take two broad forms, indirect and direct. The indirect route involves changes in positioning of ion channels, G-proteins and kinases [Burridge and Chrzanowska-Wod- nicka, 1996] through, for example, stretch [Eastwood et al., 1998] or contact guidance [Clark et al., 1991]. This leads to induction/ reduction of signaling cascades thus altering cellular behavior, for example, proliferation or differentiation. The direct form probably involves changes in tension through the cytoskeleton from relaxed morphology (rounded) to strained morphology (spread) and intermediate shapes [Ingber, 1993; Charras and Horton, 2002; Dalby, 2005]. Direct mechanotransduction has clear roles in regula- tion of blood pressure, vascular response to fluid shear stress, bone remodeling, maintenance of muscle, and perception of touch and sound [Katsumi et al., 2004]. It is known that the extracellular environ- ment can cause extremes of morphology with hydrophobic surfaces generally giving poor cellular adhesion and hence a rounded morphol- ogy [Martines et al., 2005] to grooved surfaces (topographical or chemically printed) or uni- axially stretched surfaces leading to cellular extension [Clark et al., 1991; Eastwood et al., 1998]. Chemical and topographical patterning can also be used to confine cells in shapes that ß 2007 Wiley-Liss, Inc. *Correspondence to: Matthew J. Dalby, Centre for Cell Engineering, Joseph Black Building, Institute of Biomedi- cal and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK. E-mail: m.dalby@bio.gla.ac.uk Received 5 March 2007; Accepted 6 March 2007 DOI 10.1002/jcb.21354