Skip to main content

A Method of Three-Dimensional Visualization of Molecular Processes of Apoptosis

  • Conference paper
  • First Online:
Augmented and Virtual Reality (AVR 2014)

Abstract

Apoptosis or programmed cell death plays an important role in many physiological states and diseases. Detection of apoptotic cells, tracing the development of apoptosis, drug development and regulation of apoptosis are an important parts of basic research in medicine. A large number of models have been developed that are based on the differential equations of the chemical kinetics, and can be expressed in a uniform notation using some XML-based languages, such as SBML and CellML. We describe the CellML and the simulation environment OpenCell herein. These tools can display models schematically and output results in the form of graphs showing time dependencies of component concentrations. However, at the present time we do not have a software that could represent the results of the modelling in a form of animations as well as in the form of 3-D models. Using descriptive as well as quantitative models we discuss approaches to visualize the biological processes described by the apoptosis models. The quantitative method was implemented using a 3-D visualization of the molecular biological processes modelled by chemical kinetic equations. The quantitative parameters in our visualization scheme are determined based on the kinetic equations governing the participating components, so our visualization is not only qualitative but also quantitative. To implement this visualization, the C# software and a database of 3-D forms that model molecular complexes are developed. We present 3-D visualization of the molecular processes described in the mathematical model for the mitochondria-dependent apoptosis proposed by Bagci et al. [22] as a case study.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Muchmore, S.W., Sattler, M., Liang, H., Meadows, R.P., Harlan, J.E., Yoon, H.S., Nettesheim, D., Chang, B.S., Thompson, C.B., Wong, S.-L., Ng, S.-C., Fesik, S.W.: X-ray and NMR structure of human Bcl-xL, an inhibitor of programmedиcell death. Nature 381(6580), 335–341 (1996)

    Article  Google Scholar 

  2. Green, D.R.: Means to an End: Apoptosis and other Cell Death Mechanisms, p. 250. Cold Spring Harbour Laboratory Press, NY (2010)

    Google Scholar 

  3. Antonsson, B., Conti, F., Ciavatta, A.M., Montessuit, S., Lewis, S., Martinou, I., Bernasconi, L., Bernard, A., Mermod, J.-J., Mazzei, G., Maundrell, K., Gambale, F., Sadoul, R., Martinou, J.-C.: Inhibition of Bax channel-forming activity by Bcl-2. Science 277(5324), 370–372 (1997)

    Article  Google Scholar 

  4. Minn, A.J., Vélez, P., Schendel, S.L., Liang, H., Muchmore, S.W., Fesik, S.W., Fill, M., Thompson, C.B.: Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature 385(6614), 353–357 (1997)

    Article  Google Scholar 

  5. Schendel, S.L., Xie, Z., Montal, M.O., Matsuyama, S., Montal, M., Reed, J.C.: Channel formation by antiapoptotic protein Bcl-2. Proc. Natl. Acad. Sci. U.S.A 94(10), 5113–5118 (1997)

    Article  Google Scholar 

  6. Schlesinger, P.H., Gross, A., Yin, X.-M., Yamamoto, K., Saito, M., Waksman, G., Korsmeyer, S.J.: Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. Proc. Natl. Acad. Sci. U.S.A. 94(21), 11357–11362 (1997)

    Article  Google Scholar 

  7. Peixoto, P.M., Ryu, S.-Y., Bombrun, A., Antonsson, B., Kinnally, K.W.: MAC inhibitors suppress mitochondrial apoptosis. Biochem. J. 423(3), 381–387 (2009)

    Article  Google Scholar 

  8. Czabotar, P.E., Westphal, D., Dewson, G., Ma, S., Hockings, C., Fairlie, W.D., Lee, E.F., Yao, S., Robin, A.Y., Smith, B.J., Huang, David C.S., Kluck, R.M., Adams, J.M., Colman, P.M.: Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell 152(3), 519–531 (2013)

    Article  Google Scholar 

  9. Kushnareva, Y., Andreyev, A.Y., Kuwana, T., Newmeyer, D.D.: Bax activation initiates the assembly of a multimeric catalyst that facilitates Bax pore formation in mitochondrial outer membranes. PLoS Biol. 10(9), e1001394 (2012)

    Article  Google Scholar 

  10. Souers, A.J., Leverson, J.D., Boghaert, E.R., Ackler, S.L., Catron, N.D., Chen, J., Dayton, B.D., Ding, H., Enschede, S.H., Fairbrother, W.J., Huang, D.C.S., Hymowitz, S.G., Jin, S., Khaw, S.L., Kovar, P.J., Lam, L.T., Lee, J., Maecker, H.L., Marsh, K.C., Mason, K.D., Mitten, M.J., Nimmer, P.M., Oleksijew, A., Park, C.H., Park, C.-M., Phillips, D.C., Roberts, A.W., Sampath, D., Seymour, J.F., Smith, M.L., Sullivan, G.M., Tahir, S.K., Tse, C., Wendt, M.D., Xiao, Yu., Xue, J.C., Zhang, H., Humerickhouse, R.A., Rosenberg, S.H., Elmore, S.W.: ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med. 19(2), 202–208 (2013)

    Article  Google Scholar 

  11. Muhamedyev, R., Mansharipova, A., Muhamedyeva, E.: Visualization of Biological Processes Described by Models of Apoptosis. Life Science Journal 11(10), 320–327 (2014). ISSN:1097-8135

    Google Scholar 

  12. Garny, A., Nickerson, D.P., Cooper, J., dos Santos, R.W., Miller, A.K., McKeever, S., Nielsen, P.M., Hunter, P.J.: CellML and associated tools and techniques. Phil. Trans. R. Soc. A 2008, 366 (2008). doi:10.1098/rsta.2008.0094. Published 13 September

    Google Scholar 

  13. OpenCell (May 20, 2014). http://www.cellml.org/tools/opencell/

  14. Rangamani, P., Sirovich, L.: Survival and apoptotic pathways initiated by TNF-alpha: modeling and predictions. Biotechnology and Bioengineering 97(5), 1216–1229 (2007)

    Article  Google Scholar 

  15. Bagci, E.Z., Vodovotz, Y., Billiar, T.R., Ermentrout, B., Bahar, I.: Computational insights on the competing effects of nitric oxide in regulating apoptosis (2009) (May 20, 2014). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386238/

  16. Bagci, E.Z., Vodovotz, Y., Billiar, T.R., et al.: Bistability in Apoptosis: Roles of Bax, Bcl-2 and Mitochondrial Permeability Transition Pores. Biophysical Journal 90, 1546–1559 (2006). PubMed ID: 16339882

    Article  Google Scholar 

  17. Wimalaratne, S.M., Halstead, M.D.B., Lloyd, C.M., Cooling, M.T., Crampin, E.J., Nielsen, P.F.: A method for visualizing CellML models. Bioinformatics 25(22), 3012–3019 (2009). doi:10.1093/bioinformatics/btp495

    Article  Google Scholar 

  18. Protein Data Bank (2014). http://www.rcsb.org/pdb/home/home.do

  19. Brenner, S.: The genetics of Caenorhabditis elegans. Genetics 77(1), 71–94 (1974)

    Google Scholar 

  20. Sulston, J.E., Horvitz, H.R.: Post-embryonic cell lineages of the nematode. Caenorhabditis elegans. Dev. Biol. 56(1), 110–156 (1977)

    Google Scholar 

  21. Sulston, J.E., Schierenberg, E., White, J.G., Thomson, J.N.: The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100(1), 64–119 (1983)

    Article  Google Scholar 

  22. White, J.G., Southgate, E., Thomson, J.N., Brenner, S.: The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. R. Soc. Lond. B, Biol. Scien. 314(1165), 1–340 (1986)

    Article  Google Scholar 

  23. Wang, X., Yang, C., Chai, J., Shi, Y., Xue, D.: Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science 298(5598), 1587–1892 (2002)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yevgenia A. Daineko .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this paper

Cite this paper

Muhamedyev, R.I. et al. (2014). A Method of Three-Dimensional Visualization of Molecular Processes of Apoptosis. In: De Paolis, L., Mongelli, A. (eds) Augmented and Virtual Reality. AVR 2014. Lecture Notes in Computer Science(), vol 8853. Springer, Cham. https://doi.org/10.1007/978-3-319-13969-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-13969-2_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-13968-5

  • Online ISBN: 978-3-319-13969-2

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics