title: Binding of cationic peptides (KX)4K to DPPG bilayers. Increasing the hydrophobicity of the uncharged amino acid X drives formation of membrane bound β-sheets: A DSC and FT-IR study.
abstract: The binding of cationic peptides of the sequence (KX)4K to lipid vesicles of negatively charged dipalmitoyl-phosphatidylglycerol (DPPG) was investigated by differential scanning calorimetry (DSC) and temperature dependent Fourier-transformed infrared (FT-IR) spectroscopy. The hydrophobicity of the uncharged amino acid X was changed from G (glycine) over A (alanine), Abu (α-aminobutyric acid), V (valine) to L (leucine). The binding of the peptides caused an increase of the phase transition temperature (Tm) of DPPG by up to 20°C. The shift depended on the charge ratio and on the hydrophobicity of the amino acid X. Unexpectedly, the upward shift of Tm increased with increasing hydrophobicity of X. FT-IR spectroscopy showed a shift of the CH2 stretching vibrations of DPPG to lower frequency, particularly for bilayers in the liquid-crystalline phase, indicating an ordering of the hydrocarbon chains when the peptides were bound. Changes in the lipid C=O vibrational band indicated a dehydration of the lipid headgroup region after peptide binding. (KG)4K was bound in an unordered structure at all temperatures. All other peptides formed intermolecular antiparallel β-sheets, when bound to gel phase DPPG. However, for (KA)4K and (KAbu)4K, the β-sheets converted into an unordered structure above Tm. In contrast, the β-sheet structures of (KV)4K and (KL)4K remained stable even at 80°C when bound to the liquid-crystalline phase of DPPG. Strong aggregation of DPPG vesicles occurred after peptide binding. For the aggregates, we suggest a structure, where aggregated single β-sheets are sandwiched between opposing DPPG bilayers with a dehydrated interfacial region.
authors.affiliation: Institute of Chemistry, MLU Halle-Wittenberg, von-Danckelmann-Platz 4, 06120 Halle/Saale, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Hädicke
authors.affiliation: Institute of Chemistry, MLU Halle-Wittenberg, von-Danckelmann-Platz 4, 06120 Halle/Saale, Germany. Electronic address: alfred.blume@chemie.uni-halle.de.
authors.forename: Alfred
authors.initials: A
authors.lastname: Blume
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers; D010455:Peptides / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism*; D011485:Protein Binding; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D010715:Phosphatidylglycerols; C030345:1,2-dipalmitoylphosphatidylglycerol
keywords: Cationic peptides; DPPG; Electrostatic interaction; Hydrophobic interaction; Transition temperature; β-Sheet