Skip to main content
SpringerLink
Log in

Gold nanoparticles with surface-anchored chiral poly(acryloyl-L(D)-valine) induce differential response on mesenchymal stem cell osteogenesis

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Chirality is one of the most distinctive biochemical signatures of life, and plays crucial roles in maintaining normal functions of living cells or organisms. Pioneering work from another group has demonstrated the dependency of cell differentiation on the chirality of nano-coated substrates, but the effect of the chiral surface of nanoparticles on stem cell fates has not been investigated. In this study, the influence of molecular chiral poly(acryloyl-L(D)-valine) (L(D)- PAV)-anchored gold nanoparticles (L(D)-PAV-AuNPs) on the differentiation of mesenchymal stem cells (MSCs) was investigated. Though osteogenic differentiation of MSCs was not affected by D-PAV-AuNPs, it was significantly promoted by L-PAV-AuNPs in terms of calcium deposition, alkaline phosphatase (ALP) activity, and expression of collagen type I and osteocalcin (OCN) at both mRNA and protein levels. L-PAV-AuNPs could activate the P38 mitogen-activated protein kinase (MAPK) pathway, and may exert mechanical stress on MSCs because of high amounts of internalization. These results provide new insights on surface chirality at the nanoscale as a direct regulator to guide the differentiation of MSCs, and the use of these nanomaterials for strategic regenerative medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Higuchi, A.; Ling, Q.-D.; Chang, Y.; Hsu, S.-T.; Umezawa, A. Physical cues of biomaterials guide stem cell differentiation fate. Chem. Rev. 2013, 113, 3297–3328.

    Article  Google Scholar 

  2. Langer, R.; Tirrell, D. A. Designing materials for biology and medicine. Nature 2004, 428, 487–492.

    Article  Google Scholar 

  3. Khademhosseini, A.; Vacanti, J. P.; Langer, R. Progress in tissue engineering. Sci. Am. 2009, 300, 64–71.

    Article  Google Scholar 

  4. Pittenger, M. F.; Mackay, A. M.; Beck, S. C.; Jaiswal, R. K.; Douglas, R.; Mosca, J. D.; Moorman, M. A.; Simonetti, D. W.; Craig, S.; Marshak, D. R. Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284, 143–147.

    Article  Google Scholar 

  5. Beachy, P. A.; Karhadkar, S. S.; Berman, D. M. Tissue repair and stem cell renewal in carcinogenesis. Nature 2004, 432, 324–331.

    Article  Google Scholar 

  6. Zhang, Z.-Y.; Teoh, S.-H.; Hui, J. H. P.; Fisk, N. M.; Choolani, M.; Chan, J. K. Y. The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application. Biomaterials 2012, 33, 2656–2672.

    Article  Google Scholar 

  7. Zhang, Z. Y.; Teoh, S. H.; Chong, M. S. K.; Schantz, J. T.; Fisk, N. M.; Choolani, M. A.; Chan, J. Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells 2009, 27, 126–137.

    Article  Google Scholar 

  8. Seong, J. M.; Kim, B.-C.; Park, J.-H.; Kwon, I. K.; Mantalaris, A.; Hwang, Y.-S. Stem cells in bone tissue engineering. Biomed. Mater. 2010, 5, 062001.

    Article  Google Scholar 

  9. Jiang, J. L.; Papoutsakis, E. T. Stem-cell niche based comparative analysis of chemical and nano-mechanical material properties impacting ex vivo expansion and differentiation of hematopoietic and mesenchymal stem cells. Adv. Healthc. Mater. 2013, 2, 25–42.

    Article  Google Scholar 

  10. Benoit, D. S. W.; Schwartz, M. P.; Durney, A. R.; Anseth, K. S. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat. Mater. 2008, 7, 816–823.

    Article  Google Scholar 

  11. Curran, J. M.; Chen, R.; Hunt, J. A. The guidance of human mesenchymal stem cell differentiation in vitro by controlled modifications to the cell substrate. Biomaterials 2006, 27, 4783–4793.

    Article  Google Scholar 

  12. Kilian, K. A.; Bugarija, B.; Lahn, B. T.; Mrksich, M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl. Acad. Sci. USA 2010, 107, 4872–4877.

    Article  Google Scholar 

  13. Dingal, P. C. D. P.; Wells, R. G.; Discher, D. E. Simple insoluble cues specify stem cell differentiation. Proc. Natl. Acad. Sci. USA 2014, 111, 18104–18105.

    Article  Google Scholar 

  14. Engler, A. J.; Sen, S.; Sweeney, H. L.; Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 2006, 126, 677–689.

    Article  Google Scholar 

  15. McBeath, R.; Pirone, D. M.; Nelson, C. M.; Bhadriraju, K.; Chen, C. S. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 2004, 6, 483–495.

    Article  Google Scholar 

  16. Deng, J.; Sun, M. C.; Zhu, J. Y.; Gao, C. Y. Molecular interactions of different size AuNP–COOH nanoparticles with human fibrinogen. Nanoscale 2013, 5, 8130–8137.

    Article  Google Scholar 

  17. Alkilany, A. M.; Lohse, S. E.; Murphy, C. J. The gold standard: Gold nanoparticle libraries to understand the nano–bio interface. Acc. Chem. Res. 2013, 46, 650–661.

    Article  Google Scholar 

  18. Li, W.-J.; Tuli, R.; Huang, X. X.; Laquerriere, P.; Tuan, R. S. Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials 2005, 26, 5158–5166.

    Article  Google Scholar 

  19. Xin, X. J.; Hussain, M.; Mao, J. J. Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. Biomaterials 2007, 28, 316–325.

    Article  Google Scholar 

  20. Ha, S.-W.; Weitzmann, M. N.; Beck, G. R., Jr. Bioactive silica nanoparticles promote osteoblast differentiation through stimulation of autophagy and direct association with LC3 and p62. ACS Nano 2014, 8, 5898–5910.

    Article  Google Scholar 

  21. Li, J. J.; Kawazoe, N.; Chen, G. P. Gold nanoparticles with different charge and moiety induce differential cell response on mesenchymal stem cell osteogenesis. Biomaterials 2015, 54, 226–236.

    Article  Google Scholar 

  22. Jiang, P. F.; Yu, D. H.; Zhang, W. J.; Mao, Z. W.; Gao, C. Y. Influence of bovine serum albumin coated poly(lactic-coglycolic acid) particles on differentiation of mesenchymal stem cells. RSC Adv. 2015, 5, 40924–40931.

    Article  Google Scholar 

  23. Malcolm East, J. Membrane structural biology with biochemical and biophysical foundations. Mol. Membr. Biol. 2008, 25, 584.

    Article  Google Scholar 

  24. Liu, G. F.; Zhang, D.; Feng, C. L. Control of three-dimensional cell adhesion by the chirality of nanofibers in hydrogels. Angew. Chem., Int. Ed. 2014, 53, 7789–7793.

    Article  Google Scholar 

  25. Yao, X.; Hu, Y. W.; Cao, B.; Peng, R.; Ding, J. D. Effects of surface molecular chirality on adhesion and differentiation of stem cells. Biomaterials 2013, 34, 9001–9009.

    Article  Google Scholar 

  26. Wang, X.; Gan, H.; Sun, T. L. Chiral design for polymeric biointerface: The influence of surface chirality on protein adsorption. Adv. Funct. Mater. 2011, 21, 3276–3281.

    Article  Google Scholar 

  27. Yang, X.; Gan, L. F.; Han, L.; Li, D.; Wang, J.; Wang, E. K. Facile preparation of chiral penicillamine protected gold nanoclusters and their applications in cell imaging. Chem. Commun. 2013, 49, 2302–2304.

    Article  Google Scholar 

  28. Li, Y.; Zhou, Y. L.; Wang, H. Y.; Perrett, S.; Zhao, Y. L.; Tang, Z. Y.; Nie, G. J. Chirality of glutathione surface coating affects the cytotoxicity of quantum dots. Angew. Chem., Int. Ed. 2011, 50, 5860–5864.

    Article  Google Scholar 

  29. El-Sayed, M. A. Some interesting properties of metals confined in time and nanometer space of different shapes. Acc. Chem. Res. 2001, 34, 257–264.

    Article  Google Scholar 

  30. Boisselier, E.; Astruc, D. Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chem. Soc. Rev. 2009, 38, 1759–1782.

    Article  Google Scholar 

  31. Lind, U.; Greenidge, P.; Gustafsson, J.-Å.; Wright, A. P. H.; Carlstedt-Duke, J. Valine 571 functions as a regional organizer in programming the glucocorticoid receptor for differential binding of glucocorticoids and mineralocorticoids. J. Biol. Chem. 1999, 274, 18515–18523.

    Article  Google Scholar 

  32. Li, M.; Tzagoloff, A. Assembly of the mitochondrial membrane system: Sequences of yeast mitochondrial valine and an unusual threonine tRNA gene. Cell 1979, 18, 47–53.

    Article  Google Scholar 

  33. Gilbert, S. F.; Migeon, B. R. D-valine as a selective agent for normal human and rodent epithelial cells in culture. Cell 1975, 5, 11–17.

    Article  Google Scholar 

  34. Deng, J.; Li, Z.; Yao, M. Y.; Gao, C. Y. Influence of albumin configuration by the chiral polymer-grafted gold nanoparticles. Langmuir 2016, 32, 5608–5616.

    Article  Google Scholar 

  35. Jiang, P. F.; Mao, Z. W.; Gao, C. Y. Combinational effect of matrix elasticity and alendronate density on differentiation of rat mesenchymal stem cells. Acta Biomater. 2015, 19, 76–84.

    Article  Google Scholar 

  36. Deng, J.; Zheng, H. H.; Wu, S.; Zhang, P.; Gao, C. Y. Protein adsorption and cellular uptake of AuNPs capped with alkyl acids of different length. RSC Adv. 2015, 5, 22792–22801.

    Article  Google Scholar 

  37. Gagner, J. E.; Lopez, M. D.; Dordick, J. S.; Siegel, R. W. Effect of gold nanoparticle morphology on adsorbed protein structure and function. Biomaterials 2011, 32, 7241–7252.

    Article  Google Scholar 

  38. Röcker, C.; Pötzl, M.; Zhang, F.; Parak, W. J.; Nienhaus, G. U. A quantitative fluorescence study of protein monolayer formation on colloidal nanoparticles. Nat. Nanotechnol. 2009, 4, 577–580.

    Article  Google Scholar 

  39. Huang, R. X.; Carney, R. P.; Ikuma, K.; Stellacci, F.; Lau, B. L. T. Effects of surface compositional and structural heterogeneity on nanoparticle–protein interactions: Different protein configurations. ACS Nano 2014, 8, 5402–5412.

    Article  Google Scholar 

  40. Gerlier, D.; Thomasset, N. Use of MTT colorimetric assay to measure cell activation. J. Immunol. Methods 1986, 94, 57–63.

    Article  Google Scholar 

  41. Twentyman, P. R.; Luscombe, M. A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. Br. J. Cancer 1987, 56, 279–285.

    Article  Google Scholar 

  42. Yi, C. Q.; Liu, D. D.; Fong, C.-C.; Zhang, J. C.; Yang, M. S. Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano 2010, 4, 6439–6448.

    Article  Google Scholar 

  43. Maxson, S.; Lopez, E. A.; Yoo, D.; Danilkovitch-Miagkova, A.; LeRoux, M. A. Concise review: Role of mesenchymal stem cells in wound repair. Stem Cells Trans. Med. 2012, 1, 142–149.

    Article  Google Scholar 

  44. Stanford, C. M.; Jacobson, P. A.; Eanes, E. D.; Lembke, L. A.; Midura, R. J. Rapidly forming apatitic mineral in an osteoblastic cell line (UMR 106-01 BSP). J. Biol. Chem. 1995, 270, 9420–9428.

    Article  Google Scholar 

  45. Dalby, M. J.; Gadegaard, N.; Tare, R.; Andar, A.; Riehle, M. O.; Herzyk, P.; Wilkinson, C. D. W.; Oreffo, R. O. C. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater. 2007, 6, 997–1003.

    Article  Google Scholar 

  46. Nikukar, H.; Reid, S.; Tsimbouri, P. M.; Riehle, M. O.; Curtis, A. S. G.; Dalby, M. J. Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction. ACS Nano 2013, 7, 2758–2767.

    Article  Google Scholar 

  47. Abdallah, B. M.; Jensen, C. H.; Gutierrez, G.; Leslie, R. G. Q.; Jensen, T. G.; Kassem, M. Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1. J. Bone Miner. Res. 2004, 19, 841–852.

    Article  Google Scholar 

  48. Pockwinse, S. M.; Wilming, L. G.; Conlon, D. M.; Stein, G. S.; Lian, J. B. Expression of cell growth and bone specific genes at single cell resolution during development of bone tissue-like organization in primary osteoblast cultures. J. Cell. Biochem. 1992, 49, 310–323.

    Article  Google Scholar 

  49. Blomqvist, C.; Risteli, L.; Risteli, J.; Virkkunen, P.; Sarna, S.; Elomaa, I. Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma. Br. J. Cancer 1996, 73, 1074–1079.

    Article  Google Scholar 

  50. Nakamura, A.; Dohi, Y.; Akahane, M.; Ohgushi, H.; Nakajima, H.; Funaoka, H.; Takakura, Y. Osteocalcin secretion as an early marker of in vitro osteogenic differentiation of rat mesenchymal stem cells. Tissue Eng. Part C: Methods 2009, 15, 169–180.

    Article  Google Scholar 

  51. Kratchmarova, I.; Blagoev, B.; Haack-Sorensen, M.; Kassem, M.; Mann, M. Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation. Science 2005, 308, 1472–1477.

    Article  Google Scholar 

  52. Zhang, W.; Liu, H. T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2002, 12, 9–18.

    Article  Google Scholar 

  53. Chang, L. F.; Karin, M. Mammalian MAP kinase signalling cascades. Nature 2001, 410, 37–40.

    Article  Google Scholar 

  54. Zeng, H. F.; Li, X. Y.; Xie, F.; Teng, L.; Chen, H. F. Dextran-coated fluorapatite nanorods doped with lanthanides in labelling and directing osteogenic differentiation of bone marrow mesenchymal stem cells. J. Mater. Chem. B 2014, 2, 3609–3617.

    Article  Google Scholar 

  55. Choi, S. Y.; Song, M. S.; Ryu, P. D.; Lam, A. T. N.; Joo, S.-W.; Lee, S. Y. Gold nanoparticles promote osteogenic differentiation in human adipose-derived mesenchymal stem cells through the Wnt/β-catenin signaling pathway. Int. J. Nanomedicine 2015, 10, 4383–4392.

    Google Scholar 

  56. Samberg, M. E.; Loboa, E. G.; Oldenburg, S. J.; Monteiro- Riviere, N. A. Silver nanoparticles do not influence stem cell differentiation but cause minimal toxicity. Nanomedicine 2012, 7, 1197–1209.

    Article  Google Scholar 

  57. Greulich, C.; Diendorf, J.; Simon, T.; Eggeler, G.; Epple, M.; Köller, M. Uptake and intracellular distribution of silver nanoparticles in human mesenchymal stem cells. Acta Biomater. 2011, 7, 347–354.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China

    Jun Deng, Honghao Zheng, Xiaowen Zheng, Mengyun Yao, Zheng Li & Changyou Gao

Authors
  1. Jun Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Honghao Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaowen Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mengyun Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Changyou Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changyou Gao.

Electronic supplementary material

12274_2016_1239_MOESM1_ESM.pdf

Gold nanoparticles with surface-anchored chiral poly(acryloyl-L(D)-valine) induce differential response on mesenchymal stem cell osteogenesis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, J., Zheng, H., Zheng, X. et al. Gold nanoparticles with surface-anchored chiral poly(acryloyl-L(D)-valine) induce differential response on mesenchymal stem cell osteogenesis. Nano Res. 9, 3683–3694 (2016). https://doi.org/10.1007/s12274-016-1239-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-016-1239-y

Keywords

Search

Navigation