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Topographically induced self-deformation of the nuclei of cells: dependence on cell type and proposed mechanisms

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Abstract

Osteosarcoma-derived cell lines (SaOs-2, MG63) have recently been shown to deform their nucleus considerably in response to surface topography. Such a deformation had not been described previously. Here we present results on additional cell lines, including cancerous (OHS4, U2OS), immortalized (F/STRO-1+A and FHSO6) and healthy cells (HOP). The cancerous cells were found to deform extensively, the immortalized cells showed small deformations, whereas the healthy cells showed deformation only at short incubation times. These results suggest a strong link between the malignant transformation of cells and the state of the cytoskeletal network. We propose mechanisms to explain the deformation in which the cytoskeleton either pushes down on the nucleus during spreading or pulls it down upon adhesion to the pillars.

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References

  1. Su WT, Chu IM, Yang JY, Lin CD. The geometric pattern of a pillared substrate influences the cell-process distribution and shapes of fibroblasts. Micron. 2006;37:699–706.

    Article  MATH  PubMed  Google Scholar 

  2. Tan JL, Tien J, Pirone DM, Gray DS, Bhadriraju K, Chen CS. Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc Natl Acad Sci. 2003;100:1484–9.

    Article  CAS  PubMed  ADS  Google Scholar 

  3. Steinberg T, Schultz S, Spatz JP, Grabe N, Mussig E, Kohl A, et al. Early keratinocyte differentiation on micropillar interfaces. Nano Lett. 2007;7:287–94.

    Article  CAS  PubMed  ADS  Google Scholar 

  4. Thery M, Racine V, Piel M, Pépin A, Dimitrov A, Chen Y, et al. Anisotropy of cell adhesive microenvironment governs cell internal organization and orientation of polarity. PNAS. 2006;103:19771–6.

    Article  CAS  PubMed  ADS  Google Scholar 

  5. Bischofs IB, Schmidt SS, Schwarz US. Effect of adhesion geometry and rigidity on cellular force distributions. Phys Rev Lett. 2009;103:048101.

    Google Scholar 

  6. Anselme K, Bigerelle M, Noël B, Loison I, Hardouin P. Kinetic study of the expression of β-catenin, actin and vinculin during osteoblastic adhesion on grooved titanium substrates. Biomed Mater Eng. 2004;14:545–56.

    CAS  PubMed  Google Scholar 

  7. Tsai WB, Ting YC, Yang JY, Lai JY, Liu HL. Fibronectin modulates the morphology of osteoblast-like cells (MG-63) on nano-grooved substrates. J Mater Sci Mater Med. 2009;20:1367–78.

    Article  CAS  PubMed  Google Scholar 

  8. Dalby MJ, Riehle MO, Yarwood SJ, Wilkinson CD, Curtis AS. Nucleus alignment and cell signaling in fibroblasts: response to a micro-grooved topography. Exp Cell Res. 2003;284:274–82.

    Article  CAS  PubMed  Google Scholar 

  9. Davidson P, Özçelik H, Hasirci V, Reiter G, Anselme K. Micro-structured surfaces cause severe but non-detrimental deformation of the cell nucleus. Adv Mater. 2009;21:3586–90.

    Article  CAS  Google Scholar 

  10. Ingber DE. Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol. 1997;59:575–99.

    Article  CAS  PubMed  Google Scholar 

  11. Taddei A, Hediger F, Neumann FR, Gasser SM. The function of nuclear architecture: a genetic approach. Annu Rev Genet. 2004;38:305–45.

    Article  CAS  PubMed  Google Scholar 

  12. Reddy KL, Zullo JM, Bertolino E, Singh H. Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature. 2008;452:243–7.

    Article  CAS  PubMed  ADS  Google Scholar 

  13. Ben-Ze’ev A. The cytoskeleton in cancer cells. Biochim Biophys Acta. 1985;780:197–212.

    PubMed  Google Scholar 

  14. Ali SH, DeCaprio JA. Cellular transformation by SV40 large T antigen: interaction with host proteins. Semin Cancer Biol. 2001;11:15–23.

    Article  CAS  PubMed  Google Scholar 

  15. Guck J, Schinkinger S, Lincoln B, Wottawah F, Ebert S, Romeyke M, et al. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys J. 2005;88:3689–98.

    Article  CAS  PubMed  Google Scholar 

  16. Anselme K, Broux O, Noël B, Bouxin B, Bascoulergue G, Dudermel A-F, et al. In vitro control of human bone marrow stromal cells for bone tissue engineering. Tissue Eng. 2002;8:941–53.

    Article  CAS  PubMed  Google Scholar 

  17. Oyajobi BO, Lomri A, Hott M, Marie PJ. Isolation and characterization of human clonogenic osteoblast progenitors immunoselected from fetal bone marrow stroma using STRO-1 monoclonal antibody. J Bone Miner Res. 1999;14:351–61.

    Article  CAS  PubMed  Google Scholar 

  18. Fromigue O, Kheddoumi N, Lomri A, Marie PJ, Body JJ. Breast cancer cells release factors that induced apoptosis in human bone marrow stromal cells. J Bone Miner Res. 2001;16:1600–10.

    Article  CAS  PubMed  Google Scholar 

  19. Rodan GA, Majeska RJ. Phenotypic maturation of osteoblastic osteosarcoma cells in culture. Prog Clin Biol Res. 1982;110 Pt B:249–59.

    CAS  PubMed  Google Scholar 

  20. Bidwell JP, Alvarez M, Feister H, Onyia J, Hock J. Nuclear matrix proteins and osteoblast gene expression. J Bone Miner Res. 1998;13:155–67.

    Article  CAS  PubMed  Google Scholar 

  21. Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol. 2009;10:75–82.

    Article  CAS  PubMed  Google Scholar 

  22. Frolov VA, Zimmerberg J. Shaping biological matter. Nat Mater. 2009;8:173–4.

    Article  CAS  PubMed  ADS  Google Scholar 

  23. Comer KA, Dennis PA, Armstrong L, Catino JJ, Kastan MB, Kumar CC. Human smooth muscle alpha-actin gene is a transcriptional target of the p53 tumor suppressor protein. Oncogene. 1998;16:1299–308.

    Article  CAS  PubMed  Google Scholar 

  24. Heessen S, Leonchiks A, Issaeva N, Sharipo A, Selivanova G, Masucci MG, et al. Functional p53 chimeras containing the Epstein-Barr virus Gly-Ala repeat are protected from Mdm2- and HPV-E6-induced proteolysis. Proc Natl Acad Sci U S A. 2002;99:1532–7.

    Article  CAS  PubMed  ADS  Google Scholar 

  25. Ochalek T, Nordt FJ, Tullberg K, Burger MM. Correlation between cell deformability and metastatic potential in B16–F1 melanoma cell variants. Cancer Res. 1988;48:5124–8.

    CAS  PubMed  Google Scholar 

  26. Docheva D, Padula D, Popov C, Mutschler W, Clausen-Schaumann H, Schieker M. Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy. J Cell Mol Med. 2008;12:537–52.

    Article  PubMed  Google Scholar 

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Acknowledgments

Financial support provided through the European Community’s ‘‘Marie Curie Actions’’ under contract MRTN-CT-2004-005516 (BioPolySurf). V. H. also acknowledges the support of TUBITAK (the Scientific and Technical Research Council of Turkey) through the project Nanobiomat (TBAG 105T508). We also acknowledge Prof. A. Aydinli of Bilkent University for the patterned templates.

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Correspondence to Karine Anselme.

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Davidson, P.M., Fromigué, O., Marie, P.J. et al. Topographically induced self-deformation of the nuclei of cells: dependence on cell type and proposed mechanisms. J Mater Sci: Mater Med 21, 939–946 (2010). https://doi.org/10.1007/s10856-009-3950-7

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  • DOI: https://doi.org/10.1007/s10856-009-3950-7

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