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The influence of nanotopography on organelle organization and communication

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Abstract

Cellular differentiation can be affected by the extracellular environment, particularly extracellular substrates. The nanotopography of the substrate may be involved in the mechanisms of cellular differentiation in vivo. Organelles are major players in various cellular functions; however, the influence of nanotopography on organelles has not yet been elucidated. In the present study, a micropit-nanotube topography (MNT) was fabricated on the titanium surface, and organelle-specific fluorescent probes were used to detect the intracellular organelle organization of MG63 cells. Communication between organelles, identified by organelle-specific GTPase expression, was evaluated by quantitative polymerase chain reaction and western blotting. Transmission electron microscopy was performed to evaluate the organelle structure. There were no significant differences in organelle distribution or number between the MNT and flat surface. However, organelle-specific GTPases on the MNT were dramatically downregulated. In addition, obvious endoplasmic reticulum lumen dilation was observed on the MNT surface, and the unfolded protein response (UPR) was also initiated. Regarding the relationships among organelle trafficking, UPR, and osteogenic differentiation, our findings may provide important insights into the signal transduction induced by nanotopography.

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References

  1. Bettinger, C. J.; Langer, R.; Borenstein, J. T. Engineering substrate topography at the micro- and nanoscale to control cell function. Angew. Chem., Int. Ed. 2009, 48, 5406–5415.

    Article  Google Scholar 

  2. Park, J.; Bauer, S.; von der Mark, K.; Schmuki, P. Nanosize and vitality: TiO2 nanotube diameter directs cell fate. Nano Lett. 2007, 7, 1686–1691.

    Article  Google Scholar 

  3. Park, J.; Bauer, S.; Schlegel, K. A.; Neukam, F. W.; von der Mark, K.; Schmuki, P. TiO2 nanotube surfaces: 15 nm—An optimal length scale of surface topography for cell adhesion and differentiation. Small 2009, 5, 666–671.

    Article  Google Scholar 

  4. Wang, W.; Zhao, L. Z.; Ma, Q. L.; Wang, Q. T.; Chu, P. K.; Zhang, Y. M. The role of the Wnt/β-catenin pathway in the effect of implant topography on MG63 differentiation. Biomaterials 2012, 33, 7993–8002.

    Article  Google Scholar 

  5. Wang, W.; Liu, Q.; Zhang, Y. M.; Zhao, L. Z. Involvement of ILK/ERK1/2 and ILK/p38 pathways in mediating the enhanced osteoblast differentiation by micro/nanotopography. Acta Biomater. 2014, 10, 3705–3715.

    Article  Google Scholar 

  6. Liu, Q.; Wang, W.; Zhang, L.; Zhao, L.; Song, W.; Duan, X.; Zhang, Y. Involvement of N-cadherin/β-catenin interaction in the micro/nanotopography induced indirect mechanotransduction. Biomaterials 2014, 35, 6206–18.

    Article  Google Scholar 

  7. Buxboim, A.; Ivanovska, I. L.; Discher, D. E. Matrix elasticity, cytoskeletal forces and physics of the nucleus: How deeply do cells “feel” outside and in? J. Cell Sci. 2010, 123, 297–308.

    Article  Google Scholar 

  8. Fu, J. P.; Wang, Y. K.; Yang, M. T.; Desai, R. A.; Yu, X.; Liu, Z. J.; Chen, C. S. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat. Methods 2010, 7, 733–736.

    Article  Google Scholar 

  9. Buxboim, A.; Discher, D. E. Stem cells feel the difference. Nat. Methods 2010, 7, 695–697.

    Article  Google Scholar 

  10. Swift, J.; Ivanovska, I. L.; Buxboim, A.; Harada, T.; Dingal, P. C. D. P.; Pinter, J.; Pajerowski, J. D.; Spinler, K. R.; Shin, J. W.; Tewari, M. et al. Nuclear lamin—A scales with tissue stiffness and enhances matrix-directed differentiation. Science 2013, 341, 1240104.

    Article  Google Scholar 

  11. Taniguchi, T.; Kido, S.; Yamauchi, E.; Abe, M.; Matsumoto, T.; Taniguchi, H. Induction of endosomal/lysosomal pathways in differentiating osteoblasts as revealed by combined proteomic and transcriptomic analyses. FEBS Lett. 2010, 584, 3969–3974.

    Article  Google Scholar 

  12. An, J. H.; Yang, J.-Y.; Ahn, B. Y.; Cho, S. W.; Jung, J. Y.; Cho, H. Y.; Cho, Y. M.; Kim, S. W.; Park, K. S.; Kim, S. Y. et al. Enhanced mitochondrial biogenesis contributes to Wnt induced osteoblastic differentiation of C3H10T1/2 cells. Bone 2010, 47, 140–150.

    Article  Google Scholar 

  13. Nabavi, N.; Urukova, Y.; Cardelli, M.; Aubin, J. E.; Harrison, R. E. Lysosome dispersion in osteoblasts accommodates enhanced collagen production during differentiation. J. Biol. Chem. 2008, 283, 19678–19690.

    Article  Google Scholar 

  14. Behnia, R.; Munro, S. Organelle identity and the signposts for membrane traffic. Nature 2005, 438, 597–604.

    Article  Google Scholar 

  15. Munro, S. Organelle identity and the organization of membrane traffic. Nat. Cell Biol. 2004, 6, 469–472.

    Article  Google Scholar 

  16. Sun, X. Y.; Driscoll, M. K.; Guven, C.; Das, S.; Parent, C. A.; Fourkas, J. T.; Losert, W. Asymmetric nanotopography biases cytoskeletal dynamics and promotes unidirectional cell guidance. Proc. Natl. Acad. Sci. USA 2015, 112, 12557–12562.

    Article  Google Scholar 

  17. Kim, D. H.; Provenzano, P. P.; Smith, C. L.; Levchenko, A. Matrix nanotopography as a regulator of cell function. J. Cell Biol. 2012, 197, 351–360.

    Article  Google Scholar 

  18. Oakley, C.; Brunette, D. M. The sequence of alignment of microtubules, focal contacts and actin filaments in fibroblasts spreading on smooth and grooved titanium substrata. J. Cell Sci. 1993, 106, 343–354.

    Google Scholar 

  19. Cooper, G. M. The Cell: A Molecular Approach, 2nd ed; Sinauer Associates: Sunderland, MA, USA, 2000.

    Google Scholar 

  20. Caviston, J. P.; Holzbaur, E. L. F. Microtubule motors at the intersection of trafficking and transport. Trends Cell Biol. 2006, 16, 530–537.

    Article  Google Scholar 

  21. Zhao, L. Z.; Mei, S. L.; Wang, W.; Chu, P. K.; Wu, Z. F.; Zhang, Y. M. The role of sterilization in the cytocompatibility of titania nanotubes. Biomaterials 2010, 31, 2055–2063.

    Article  Google Scholar 

  22. Zhao, L. Z.; Mei, S. L.; Chu, P. K.; Zhang, Y. M.; Wu, Z. F. The influence of hierarchical hybrid micro/nano-textured titanium surface with titania nanotubes on osteoblast functions. Biomaterials 2010, 31, 5072–5082.

    Article  Google Scholar 

  23. Zhao, L. Z.; Liu, L.; Wu, Z. F.; Zhang, Y. M.; Chu, P. K. Effects of micropitted/nanotubular titania topographies on bone mesenchymal stem cell osteogenic differentiation. Biomaterials 2012, 33, 2629–2641.

    Article  Google Scholar 

  24. van Bergeijk, P.; Adrian, M.; Hoogenraad, C. C.; Kapitein, L. C. Optogenetic control of organelle transport and positioning. Nature 2015, 518, 111–114.

    Article  Google Scholar 

  25. Kasap, M.; Karaoz, E.; Akpinar, G.; Aksoy, A.; Erman, G. A unique Golgi apparatus distribution may be a marker for osteogenic differentiation of hDP-MSCs. Cell Biochem. Funct. 2011, 29, 489–495.

    Article  Google Scholar 

  26. Nørgaard, R.; Kassem, M.; Rattan, S. I. S. Heat shockinduced enhancement of osteoblastic differentiation of htertimmortalized mesenchymal stem cells. Ann. N. Y. Acad. Sci. 2006, 1067, 443–447.

    Article  Google Scholar 

  27. Hamamura, K.; Yokota, H. Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone remodeling. FEBS Lett. 2007, 581, 1769–1774.

    Article  Google Scholar 

  28. Wagegg, M.; Gaber, T.; Lohanatha, F. L.; Hahne, M.; Strehl, C.; Fangradt, M.; Tran, C. L.; Schönbeck, K.; Hoff, P.; Ode, A. et al. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner. PLoS One 2012, 7, e46483.

    Article  Google Scholar 

  29. Pantovic, A.; Krstic, A.; Janjetovic, K.; Kocic, J.; Harhaji-Trajkovic, L.; Bugarski, D.; Trajkovic, V. Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. Bone 2013, 52, 524–531.

    Article  Google Scholar 

  30. Levine, A. Regulation of stress responses by intracellular vesicle trafficking? Plant Physiol. Biochem. 2002, 40, 531–535.

    Article  Google Scholar 

  31. Oslowski, C. M.; Urano, F. Measuring er stress and the unfolded protein response using mammalian tissue culture system. Methods Enzymol. 2011, 490, 71–92.

    Article  Google Scholar 

  32. Tsai, Y. C.; Weissman, A. M. The unfolded protein response, degradation from the endoplasmic reticulum, and cancer. Genes Cancer 2010, 1, 764–778.

    Article  Google Scholar 

  33. Amodio, G.; Venditti, R.; De Matteis, M. A.; Moltedo, O.; Pignataro, P.; Remondelli, P. Endoplasmic reticulum stress reduces COPII vesicle formation and modifies Sec23a cycling at ERESs. FEBS Lett. 2013, 587, 3261–3266.

    Article  Google Scholar 

  34. Oh-hashi, K.; Kunieda, R.; Hirata, Y.; Kiuchi, K. Biosynthesis and secretion of mouse cysteine-rich with EGF-like domains 2. FEBS Lett. 2011, 585, 2481–2487.

    Article  Google Scholar 

  35. Murakami, T.; Saito, A.; Hino, S.; Kondo, S.; Kanemoto, S.; Chihara, K.; Sekiya, H.; Tsumagari, K.; Ochiai, K.; Yoshinaga, K. et al. Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation. Nat. Cell Biol. 2009, 11, 1205–1211.

    Article  Google Scholar 

  36. Schuck, S.; Prinz, W. A.; Thorn, K. S.; Voss, C.; Walter, P. Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response. J. Cell Biol. 2009, 187, 525–536.

    Article  Google Scholar 

  37. Lai, E.; Teodoro, T.; Volchuk, A. Endoplasmic reticulum stress: Signaling the unfolded protein response. Physiology 2007, 22, 193–201.

    Article  Google Scholar 

  38. Tsang, K. Y.; Chan, D.; Bateman, J. F.; Cheah, K. S. E. In vivo cellular adaptation to ER stress: Survival strategies with double-edged consequences. J. Cell Sci. 2010, 123, 2145–2154.

    Article  Google Scholar 

  39. Tabas, I.; Ron, D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol. 2011, 13, 184–190.

    Article  Google Scholar 

  40. Sano, R.; Reed, J. C. ER stress-induced cell death mechanisms. Biochim. Biophys. Acta 2013, 1833, 3460–3470.

    Article  Google Scholar 

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Authors and Affiliations

  1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, 710032, China

    Wen Song, Mengqi Shi, Bei Chang & Yumei Zhang

  2. Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, 8000, Denmark

    Mingdong Dong

Authors
  1. Wen Song
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  2. Mengqi Shi
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  3. Bei Chang
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  4. Mingdong Dong
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  5. Yumei Zhang
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Correspondence to Mingdong Dong or Yumei Zhang.

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These authors contributed equally to this work.

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Song, W., Shi, M., Chang, B. et al. The influence of nanotopography on organelle organization and communication. Nano Res. 9, 2433–2444 (2016). https://doi.org/10.1007/s12274-016-1129-3

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  • DOI: https://doi.org/10.1007/s12274-016-1129-3

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