The role of microtopography in cellular mechanotransduction

McNamara, Laura E.; Burchmore, Richard; Riehle, Mathis O.; Herzyk, Paweł; Biggs, Manus; Wilkinson, C. D. W.; Curtis, Adam; Dalby, Matthew J.

doi:10.1016/j.biomaterials.2011.11.047

Cited by 138 publications

(107 citation statements)

References 53 publications

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“…In tissue engineering, the surface properties of biological materials usually impose crucial impacts on cell culture, 7 healing of wounds, 8 and tissue restoration and reconstruction. 9 Specifically, cell behavior can be manipulated by altering their material properties, including chemical, 10,11 nonmechanical physical, 12,13 and mechanical properties in vitro.…”

Section: Introductionmentioning

confidence: 99%

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

Tian¹,

Qin²,

Wu³

et al. 2015

IJN

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Cells respond to their surroundings through an interactive adhesion process that has direct effects on cell proliferation and migration. This research was designed to investigate the effects of TiO 2 nanotubes with different topographies and structures on the biological behavior of cultured cells. The results demonstrated that the nanotube diameter, rather than the crystalline structure of the coatings, was a major factor for the biological behavior of the cultured cells. The optimal diameter of the nanotubes was 20 nm for cell adhesion, migration, and proliferation in both glioma and osteosarcoma cells. The expression levels of vitronectin and phosphor-focal adhesion kinase were affected by the nanotube diameter; therefore, it is proposed that the responses of vitronectin and phosphor-focal adhesion kinase to the nanotube could modulate cell fate. In addition, the geometry and size of the nanotube coating could regulate the degree of expression of acetylated α-tubulin, thus indirectly modulating cell migration behavior. Moreover, the expression levels of apoptosis-associated proteins were influenced by the topography. In conclusion, a nanotube diameter of 20 nm was the critical threshold that upregulated the expression level of Bcl-2 and obviously decreased the expression levels of Bax and caspase-3. This information will be useful for future biomedical and clinical applications.

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Section: Introductionmentioning

confidence: 99%

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

Tian¹,

Qin²,

Wu³

et al. 2015

IJN

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“…Cellular geometry has been shown to influence nuclear deformation, cytoskeleton reorganization, chromatin compaction, gene expression, growth, apoptosis, and cell division (1)(2)(3)(4)(5)(6)(7). Other physical cues such as substrate stretching, fluid flow, substrate rigidity, and cellular topography have also been shown to alter cellular morphology, nuclear architecture, and gene expression (8)(9)(10)(11). Regulation of gene expression requires posttranslational modifications of histone tails (12), which alter higher-order chromatin assembly and, hence, the accessibility of gene-regulatory sites by transcriptional machinery (13).…”

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confidence: 99%

Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility

Jain

Iyer

Kumar

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

313

309

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Physical forces in the form of substrate rigidity or geometrical constraints have been shown to alter gene expression profile and differentiation programs. However, the underlying mechanism of gene regulation by these mechanical cues is largely unknown. In this work, we use micropatterned substrates to alter cellular geometry (shape, aspect ratio, and size) and study the nuclear mechanotransduction to regulate gene expression. Genome-wide transcriptome analysis revealed cell geometry-dependent alterations in actin-related gene expression. Increase in cell size reinforced expression of matrix-related genes, whereas reduced cell-substrate contact resulted in up-regulation of genes involved in cellular homeostasis. We also show that large-scale changes in geneexpression profile mapped onto differential modulation of nuclear morphology, actomyosin contractility and histone acetylation. Interestingly, cytoplasmic-to-nuclear redistribution of histone deacetylase 3 modulated histone acetylation in an actomyosin-dependent manner. In addition, we show that geometric constraints altered the nuclear fraction of myocardin-related transcription factor. These fractions exhibited hindered diffusion time scale within the nucleus, correlated with enhanced serum-response element promoter activity. Furthermore, nuclear accumulation of myocardin-related transcription factor also modulated NF-κB activity. Taken together, our work provides modularity in switching gene-expression patterns by cell geometric constraints via actomyosin contractility.cell matrix interaction | substrate geometry | MRTF-A signaling | chromatin remodelling | transcription control C ells within the local tissue microenvironment acquire nonrandom geometrical organization by cell-matrix and cell-cell interaction. Cellular geometry has been shown to influence nuclear deformation, cytoskeleton reorganization, chromatin compaction, gene expression, growth, apoptosis, and cell division (1-7). Other physical cues such as substrate stretching, fluid flow, substrate rigidity, and cellular topography have also been shown to alter cellular morphology, nuclear architecture, and gene expression (8-11). Regulation of gene expression requires posttranslational modifications of histone tails (12), which alter higher-order chromatin assembly and, hence, the accessibility of gene-regulatory sites by transcriptional machinery (13). In addition, cytoplasmic to nuclear shuttling of transcription factors (TFs) and cofactors are key signaling intermediates rendering specificity. Some of these factors include NF-κB, STAT, and myocardin-related transcription factor (MRTF-A) (14-16). The transcription coactivator yes-associated protein (YAP)/transcription coactivator with PDZ binding domain (TAZ) and MRTF-A have been implicated in nuclear mechanotransduction (17)(18)(19). In a recent study, alterations in cell shape were shown to influence mesenchymal stem cell differentiation (20). However, the mechanisms underlying geometric control of gene expression by the modulation of cytoplasmi...

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“…Adhesion dynamics induce complex regulation of biochemical reactions such as integrin binding to the extracellular matrix. Extracellular or intracellular physical pulling forces on focal adhesions induce tyrosinephosphorylation of the GPTase Rho initiating their growth and strengthening by the recruitment of proteins McNamara et al, 2010), which illustrates the mechanosensitivity of the focal adhesion sites. In our study, we analysed the focal adhesions of hMSCs on TCPS by staining vinculin, which links integrin to the actin CSK.…”

Section: Discussionmentioning

confidence: 99%

“…Several authors have studied experimentally the mechanics of cell adhesion by determining the magnitude of force at FAPs and the distribution of stress fibres (Green et al, 1986;Jean, 1999;Deguchi et al, 2006;Milan et al, 2007). Mechanical models based on tensegrity have also been proposed to relate the internal tension to the adhesion conditions (Kurachi et al, 1995;Balaban et al, 2001;Brangwynne et al, 2006;Dubois and Jean, 2006;McNamara et al, 2010). These models predict deformation and spatial rearrangement of CSK filaments.…”

Section: J-l Milan Et Al Mechanotransduction During Msc Adhesionmentioning

confidence: 99%

“…These levels of membrane deformation computed in the CDM model are those sensed by ion channels, which would make it possible to quantify the effect of direct mechanotransduction on calcium entry into the nucleus. Besides, deformation of the nucleus induces repositioning of chromosomes and so affects gene transcription, as observed by McNamara in confining the nucleus by the CSK and substrate micro-grooved topography (McNamara et al, 2012). Mechanosensors may be also introduced into the cell model at focal adhesion complexes or located on nodes of the CSK network.…”

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confidence: 99%

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Computational model combined with in vitro experiments to analyse mechanotransduction during mesenchymal stem cell adhesion

Milan¹,

Lavenus²,

Pilet³

et al. 2013

eCM

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The shape that stem cells reach at the end of adhesion process influences their differentiation. Rearrangement of cytoskeleton and modification of intracellular tension may activate mechanotransduction pathways controlling cell commitment. In the present study, the mechanical signals involved in cell adhesion were computed in in vitro stem cells of different shapes using a single cell model, the so-called Cytoskeleton Divided Medium (CDM) model. In the CDM model, the filamentous cytoskeleton and nucleoskeleton networks were represented as a mechanical system of multiple tensile and compressive interactions between the nodes of a divided medium. The results showed that intracellular tonus, focal adhesion forces as well as nuclear deformation increased with cell spreading. The cell model was also implemented to simulate the adhesion process of a cell that spreads on protein-coated substrate by emitting filopodia and creating new distant focal adhesion points. As a result, the cell model predicted cytoskeleton reorganisation and reinforcement during cell spreading. The present model quantitatively computed the evolution of certain elements of mechanotransduction and may be a powerful tool for understanding cell mechanobiology and designing biomaterials with specific surface properties to control cell adhesion and differentiation. Keywords:Mesenchymal stem cells; cell adhesion; cell morphology; computational cell adhesion model; cytoskeleton; mechanical forces; mechanotransduction. IntroductionCell adhesion is fundamental in the field of biomaterials. Especially in orthopaedics, it is crucial for prosthesis osseointegration (Lavenus et al., 2010). Osteoblasts need to adhere on the implant to synthesise the bone tissue that is directly connected to it without the intervening soft tissue. Moreover, stem cells, which are recruited to heal the implant interface, adhere on the surface and differentiate depending, among other factors, on their adherent morphology. For instance, stem cells which reach at the end of adhesion round, elongated or branched shapes depending on substrate topography or stiffness, differentiate preferentially into adipocytes, fibroblasts or osteoblasts, respectively (McBeath et al., 2004;Engler et al., 2006). Therefore, biomaterial surface must promote adhesion of stem cells and their differentiation into the desired phenotype so as to synthesise a periprosthetic tissue, ensuring efficient and viable biomaterial integration. Biomaterials that mimic the natural composition of the extracellular matrix have been developed. They are composed of a biological phase or are coated with RGD complex and showed positive effects on cell adhesion (Von der Mark et al., 2010). Topography and surface chemistry, which play a key role in cell adhesion, may be controlled using nanotechnology. This announces the development of new implant surfaces with predictable tissue-integrative properties (Le Guéhennec et al., 2007;Lavenus et al., 2010).Cell adhesion results from the creation of several discrete focal a...

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The role of microtopography in cellular mechanotransduction

Cited by 138 publications

References 53 publications

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility

Computational model combined with in vitro experiments to analyse mechanotransduction during mesenchymal stem cell adhesion

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