Skip to main content

Journal for Biophysical Chemistry

Biointerphases Cover Image

Phase separation of phospholipid multilayers incorporated with cell penetrating peptides

Abstract

We used X-ray reflectivity to investigate the structures of phospholipid multilayers with transcription-activating-factor-derived peptide (TDP) as a function of the membrane charge density. Mixed phospholipid multilayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS) with different mixing ratios (C:S) were used to elucidate the various charge densities in a plasma membrane. We fixed the peptide/lipid molar ratio (P/L) and varied the DPPC/DPPS molar ratio in the mixed multilayer. In the pure DPPC multilayer, the incorporation of TDP had nearly no effect on the bilayer thickness of the mixed lipid multilayer. However, in the mixed DPPC/DPPS multilayer, the incorporation of TDP decreased the bilayer thickness, suggesting that the TDP peptide had a stronger interaction with DPPS than with DPPC and caused disorder in the lamellar structure. Combining this with the refined X-ray reflectivity (XR) data, we concluded that the TDP existed more in the headgroup region of the TDP-induced segregated DPPS in the mixed multilayer and caused significant membrane thinning.

Reference

  1. 1

    K. Simons and D. Toomre, Nat. Rev. Mol. Cell Biol. 1, 31 (2000).

    Article  CAS  Google Scholar 

  2. 2

    Z.-J. Cheng, R. D. Singh, D. L. Marks, and R. E. Pagano, Mol. Membr. Biol. 23, 101 (2006).

    Article  CAS  Google Scholar 

  3. 3

    D. A. Brown and E. London, Annu. Rev. Cell Dev. Biol. 14, 111 (1998).

    Article  CAS  Google Scholar 

  4. 4

    M. Edidin, Annu. Rev. Biophys. Biomol. Struct. 32, 257 (2003).

    Article  CAS  Google Scholar 

  5. 5

    M. Nielsen, L. Miao, J. H. Lisen, K. Jø rgensen, M. J. Zuckermann, and O. G. Mouritsen, Biochim. Biophys. Acta 1283, 170 (1996).

    Article  Google Scholar 

  6. 6

    M. L. Kraft, P. K. Weber, L. M. Longo, I. D. Hutcheon, and S. G. Boxer, Science 313, 1948 (2006).

    Article  CAS  Google Scholar 

  7. 7

    J. Huang and G. W. Feigenson, Biophys. J. 65, 1788 (1993).

    Article  CAS  Google Scholar 

  8. 8

    J. Huang, J. E. Swanson, A. R. G. Dibble, A. K. Hinderliter, and G. W. Feigenson, Biophys. J. 64, 413 (1993).

    Article  CAS  Google Scholar 

  9. 9

    T. G. Anderson and H. M. McConnell, Biophys. J. 81, 2774 (2001).

    Article  CAS  Google Scholar 

  10. 10

    C. R. Safinya, Curr. Opin. Struct. Biol. 11, 440 (2001).

    Article  CAS  Google Scholar 

  11. 11

    I. Koltover, T. Salditt, and C. R. Safinya, Biophys. J. 77, 915 (1999).

    Article  CAS  Google Scholar 

  12. 12

    I. Koltover, T. Salditt, J. O. Radler, and C. R. Safinya, Science 281, 78 (1998).

    Article  CAS  Google Scholar 

  13. 13

    H. Y. Jing, D. H. Hong, B. D. Kwak, D. J. Choi, K. Shin, C.-J. Yu, J. W. Kim, D. Y. Noh, and Y. S. Seo, Langmuir 25, 4198 (2009).

    Article  CAS  Google Scholar 

  14. 14

    S. Taguchi and N. Wakayama, Jpn. J. Appl. Phys., Part 1 41, 4987 (2002).

    Article  CAS  Google Scholar 

  15. 15

    F.-Y. Chen, M.-T. Lee, and H. W. Huang, Biophys. J. 84, 3751 (2003).

    Article  CAS  Google Scholar 

  16. 16

    M.-T. Lee, F.-Y. Chen, and H. W. Huang, Biochemistry 43, 3590 (2004).

    Article  CAS  Google Scholar 

  17. 17

    J. S. Wadia and S. F. Dowdy, Adv. Drug Deliv. Rev. 57, 579 (2005).

    Article  CAS  Google Scholar 

  18. 18

    M. Green and P. M. Loewenstein, Cell 55, 1179 (1988).

    Article  CAS  Google Scholar 

  19. 19

    A. Ziegler, P. Nervi, M. Dürrenberger, and J. Seelig, Biochemistry 44, 138 (2005).

    Article  CAS  Google Scholar 

  20. 20

    T. Harder, P. Scheiffele, P. Verkade, and K. Simons, J. Cell Biol. 141, 929 (1998).

    Article  CAS  Google Scholar 

  21. 21

    J. E. Shaw, R. F. Epand, R. M. Epand, Z. Li, R. Bittman, and C. M. Yip, Biophys. J. 90, 2170 (2006).

    Article  CAS  Google Scholar 

  22. 22

    G. Tae, H. Yang, K. Shin, S. K. Satija, and N. Torikai, J. Pept. Sci. 14, 461 (2008).

    Article  CAS  Google Scholar 

  23. 23

    S. Ludtke, K. He, and H. Huang, Biochemistry 34, 16764 (1995).

    Article  CAS  Google Scholar 

  24. 24

    S. X. Hu, H. X. Li, Q. J. Jia, Z. H. Mai, and M. Li, J. Chem. Phys. 122, 124712 (2005).

    Article  Google Scholar 

  25. 25

    L. L. Xing, D. P. Li, S. X. Hu, H. Y. Jing, H. L. Fu, Z. H. Mai, and M. Li, J. Am. Chem. Soc. 128, 1749 (2006).

    Article  CAS  Google Scholar 

  26. 26

    H. W. Huang, F.-Y. Chen, and M.-T. Lee, Phys. Rev. Lett. 92, 198304 (2004).

    Article  Google Scholar 

  27. 27

    W. H. Huang, Biophys. J. 50, 1061 (1986).

    Article  CAS  Google Scholar 

  28. 28

    S. J. Ludtke, K. He, W. T. Heller, T. A. Harroun, L. Yang, and H. W. Wuang, Biochemistry 35, 13723 (1996).

    Article  CAS  Google Scholar 

  29. 29

    H. W. Huang, Biochemistry 39, 8347 (2000).

    Article  CAS  Google Scholar 

  30. 30

    M. R. Horton, C. Reich, A. P. Gast, J. O. Rädler, and B. Nickel, Langmuir 23, 6263 (2007).

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jing, H., Kim, H., Choi, D. et al. Phase separation of phospholipid multilayers incorporated with cell penetrating peptides. Biointerphases 6, 73–78 (2011). https://doi.org/10.1116/1.3602087

Download citation