Group analysis of regulation of fibroblast genome on low-adhesion nanostructures

Dalby, Matthew J.; Gadegaard, Nikolaj; Herzyk, Paweł; Agheli, Hossein; Sutherland, Duncan S.; Wilkinson, C. D. W.

doi:10.1016/j.biomaterials.2006.11.049

Cited by 32 publications

(18 citation statements)

References 36 publications

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“…In support of this, several groups have observed a decrease in β1 expression after exposure to topographic cues or other surface modifications [32, 36]. Studies from Dalby et al using anisotropic patterns of nanoscale hexagonal pits reported a similar decrease in ECM expression from fibroblasts [37]. It is possible that surfaces with topographical cues act as a negative feedback loop to decrease the production of proteins that would otherwise act as adherence support.…”

Section: Discussionmentioning

confidence: 89%

Alterations in gene expression of human vascular endothelial cells associated with nanotopographic cues

et al. 2010

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Human cells in vivo are exposed to a topographically rich, 3-dimenisional environment which provides extracellular cues initiating a cascade of biochemical signals resulting in changes in cell behavior. One primary focus of our group is the development of biomimetic substrates with anisotropic nanoscale topography to elucidate the mechanisms by which physical surface cues are translated into biochemical signals. To investigate changes in gene expression as a result of nanotopographic cues, Human Umbilical Vein Endothelial Cells (HUVECs) were cultured on chemically identical flat and 400 nm pitch nanogrooved surfaces. After 12 hours, RNA was harvested for an Affymetrix HG U133 Plus 2.0 gene array. Of over 47,000 possible gene probes, 3171 had at least a two-fold difference in expression between the control flat and 400 nm pitch. The gene ontology groups with the most significant increase in expression are involved in protein modification and maintenance, similar to cells upregulating chaperone and protein synthesis genes in response to physical stresses. The most significant decreases in expression were observed with cell cycle proteins, including cyclins and checkpoint proteins. Extracellular matrix proteins, including integrins, collagens, and laminins, are almost uniformly down regulated on the 400 nm pitch surfaces compared to control. The down regulation of one of these genes, integrin beta 1, was confirmed via quantitative PCR. Together, these gene array data, in addition to our studies of cell behavior on nanoscale surfaces, contribute to our understanding of the signaling pathways modulated by topographical surface cues.

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Section: Discussionmentioning

confidence: 89%

Alterations in gene expression of human vascular endothelial cells associated with nanotopographic cues

et al. 2010

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“…Similarly, modifying fibroblast adhesion and changing cell shape alters cytoskeletal organization and shrinks the nucleus and nuclear lamina of cultured cells. These changes in the cytoskeleton and nuclear morphology are associated with impaired polymerase access to chromosomal territories and a concomitant reduction in gene transcription91,101–103. More convincingly, Rho-family GTPases indirectly regulate histone H4 acetylation by shifting the balance of cellular and nuclear pools of F and G actin, which in turn, modifies the association between serum response factor (SRF) and its co-activator MAL (also known as MKL1)104–106.…”

Section: Gene Expression and Forcementioning

confidence: 99%

A tense situation: forcing tumour progression

2009

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Cells within tissues are continuously exposed to physical forces including hydrostatic pressure, shear stress, and compression and tension forces. Cells dynamically adapt to force by modifying their behaviour and remodelling their microenvironment. They also sense these forces through mechanoreceptors and respond by exerting reciprocal actomyosin-and cytoskeletal-dependent cellgenerated force by a process termed 'mechanoreciprocity'. Loss of mechanoreciprocity has been shown to promote the progression of disease, including cancer. Moreover, the mechanical properties of a tissue contribute to disease progression, compromise treatment and might also alter cancer risk. Thus, the changing force that cells experience needs to be considered when trying to understand the complex nature of tumorigenesis. At a glance• Cells within tissues are continuously exposed to physical forces, including hydrostatic pressure, shear stress and compression and tension forces. The nature of these forces can change in pathologies such as cardiovascular disease and cancer.• Cells sense force through mechanoreceptors and, regardless of the type of force applied, cells respond by exerting reciprocal actomyosin-and cytoskeletondependent cell-generated force by a process termed mechanoreciprocity.• Mechanoreciprocity maintains tensional homeostasis in the tissue and is necessary for development and tissue-specific differentiation. Its loss promotes disease progression, including liver fibrosis, atherosclerosis and cancer. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript• Cells dynamically adapt to force by modifying their behaviour and remodelling their microenvironment. This adaptation probably involves a combination of epigenetic chromatin remodelling events and direct physical links between the matrix and nucleus that regulate gene expression. These gene-regulatory processes are altered in diseases such as cancer.• Breast cancer is characterized by changes in cellular rheology and tissue level forces, a stiffening of the tissue and a progressive loss of tensional homeostasis that has been exploited to detect tumours. The mechanical properties of a tissue contribute to disease progression, compromise treatment and might also alter cancer risk.Force modulates cell fate and directs tissue development and post-natal function. Although we know much about the biochemical pathways that direct cell behaviour, by comparison we know less about how force can regulate cell fate and tissue phenotype. Nevertheless, cells in tissues such as the heart, lung and skeleton encounter nanoscale to macroscale forces that are integral to their function. The nature of these tissue-associated forces can be parallel, such as the shear stress induced by blood flow on a vessel wall, or perpendicular, such as the compressive or tensile stress induced by weight bearing on bone. In fact, all cells, including those incorporated into traditionally mechanically static tissues, such as the breast or the brain, are exposed to isometric forc...

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“…In the past it has been shown that when mammalian cells bind to surfaces, the detailed surface topography influences the cell behaviour with respect to processes such as adhesion, orientation, differentiation, proliferation, changes in contact guidance, cytoskeletal organisation, focal adhesion point organization, apoptosis, macrophage activation, and gene expression [1][2][3][4][5][6][7][8][9][10][11]. Several papers have indicated that phosphorylation, expression, and translocation of transcription factors are factors that play a major role in the cellular response when cells are growing on micro-and nanostructured surfaces.…”

Section: Introductionmentioning

confidence: 99%

The use of combinatorial topographical libraries for the screening of enhanced osteogenic expression and mineralization

et al. 2009

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Group analysis of regulation of fibroblast genome on low-adhesion nanostructures

Cited by 32 publications

References 36 publications

Alterations in gene expression of human vascular endothelial cells associated with nanotopographic cues

Alterations in gene expression of human vascular endothelial cells associated with nanotopographic cues

A tense situation: forcing tumour progression

The use of combinatorial topographical libraries for the screening of enhanced osteogenic expression and mineralization

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