Interactions of Peptides with Cell Membranes

All living systems contain a range of asymmetric environments such as those generated by electric fields, phase boundaries or those found at the surface of molecular aggregates within the aqueous environment.


An interface of increasing importance is that which occurs at the surface of biological membrane structures used to compartmentalise cellular and intracellular domains. The function of many biologically active molecules is dependent upon the amphiphilic structure induced by the anisotropy of these lipid-water interfaces, either because the membrane is the site of action or due to their physicochemical characteristics which determines their translocation across the bilayer and their subsequent compartmentalisation within the cell.

Research is aimed at assisting the design of peptide based therapeutics. For example, a-helical antimicrobial peptides (a-AMPs), show great potential for development as novel antibiotics. The interactions of aurein 1.2, a defence peptide, with T98G glioblastoma cell membranes are studied. The peptide induced maximal surface pressure changes of circa 9 mN m-1 in monolayers of endogenous T98G membrane lipid. Reducing monolayer anionic lipid showed a positive correlation (R2 = 0.91) with decreases in maximal surface pressure changes induced by aurein 1.2 (circa 3 mN m-1 in the absence of anionic lipid). Cancer cell membrane invasion by the peptide therefore appears not to be mediated by lipid receptors or specific lipid requirements but rather a general requirement for anionic lipid and/or other negatively charged membrane components.

Individually mutating the phenylalanine residues of another aurein peptide, aurein 2.5 to leucine had no major effect on the levels of phosphatidylglycerol and phosphatidylethanolamine interactions, suggesting that these residues are not essential to the membrane interactions of the peptide, contrasting to other aureins where corresponding phenylalanine residues are required for efficient membrane interaction and antibacterial activity. This difference in the requirement maybe related to the surface architecture as proposed by the concept of the molecular perturbation potential.


Related Publications


  • Biophysics

     

    2011

     

    • Dennison, S.R. and Phoenix, D.A. 2011. Influence of C-terminal amidation on efficacy of modelin-5. Biochemistry. 50(9) 1514-1523

    • Harris, F, Dennison, S.R. and Phoenix, D.A. 2011. Anionic antimicrobial peptides from eukaryotic organisms and their mechanisms of action. Current Chemical Biology. 5(2) 142-153

    • Harris, F., Dennison, S.R. and Phoenix 2011 On the selectivity and efficacy of defence peptides with respect to cancer cells. Medicinal Research Reviews

    • Dennison, SR, Harris, F and Phoenix (2010) A langmuir approach using on monolayer interactions to investigate surface active peptides. Protein and Peptide Science. Volume 17, Number 11,  Pages: 1363-1675

     

    2010

    • Dennison, SR. Harris, F. Bhatt, T. Singh, J and  Phoenix, D.A. (2010) A theoretical analysis of secondary structural characteristics of anticancer peptides Molecular and cellular biochemistry.  Volume 333, Numbers 1-2 pp 129-135

    • Dennison, S.R. and Phoenix, D. A (2010) – Guest editors PPL Vol 17 issue 11

    •  Harris, F, Dennison, SR and Phoenix DA (2009) Anionic antimicrobial peptides from eukaryotic organisms. Current Protein and Peptide Science. Volume 10, Number 6, pp. 585-606

    2009

    • Dennison, SR. Harris, F. Bhatt, T. Singh, J and  Phoenix, D.A. (2009)The effect of C-terminal amidation on the efficacy and selectivity of antimicrobial and anticancer peptides. Molecular and cellular biochemistry2009, vol. 332, no1-2, pp. 43-50

    • Dennison, S.R., Harris, F & Phoenix, D.A. (2009) A Study on the Importance of Phenylaniline for Aurein functionality. Protein and Peptide Letters. Volume 16, Number 12, , pp. 1455-1458(4)

    • Dennison, S.R., Morton, L.H.G, Shorrocks, A.J, Harris, F. & Phoenix, D.A. (2009) A study on the interactions of Aurein 2.5 with bacterial membranes. Colloids and Surfaces B: Biointerfaces, Volume 68, Issue 2, 1 2009, pages 225-230

    2008

    • Dennison, S. R., Soo Kim, Y. ChaH. J, & Phoenix, D.A. (2008) Investigations into the ability of the peptide, HAL18, to interact with bacterial membranesEuropean Journal Biophysics. volume 38, isuue 1, pages 37-43

    • Dennison, S. R., Morton, L.G.H., Harris, F & Phoenix, D. A., (2008)The impact of membrane lipid composition on antimicrobial function of an α-helical peptide Chemistry and Physics of Lipids, Volume 151, Issue 2, February 2008, Pages 92-102

    2007

    • Dennison, S. R., Harris, F., Brandenburg, K & Phoenix, D. A. (2007) Characterization of the N-terminal segment used by the barley yellow dwarf virus movement protein to promote interaction with the nuclear membrane of host plant cellsPeptides, Volume 28, Issue 11, November 2007, Pages 2091-2097

    • Dennison, S. R., Baker, R. D., Nicholl, I.D. & Phoenix, D. A. (2007) Interactions of cell penetrating peptide Tat with model membranes: A biophysical study Biochemical and Biophysical Research Communications, Volume 363, Issue 1, 9 November 2007, Pages 178-182

    • Dennison, S.R., Morton, L.H.G., Harris, F., & Phoenix, D.A. (2007). Antimicrobial properties of a lipid interactive α-helical peptide VP1 against Staphylococcus aureus bacteria. Biophysical Chemistry. Volume 129, Issues 2-3, September 2007, Pages 279-283

    • Dennison, S. R., Harris, F., and Phoenix D.A. (2007).The interactions of aurein 1.2 with cancer cell membranes Biophysical Chemistry. 127 (1-2), 78-83.

       



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