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riDOM, a cell penetrating peptide. Interaction with phospholipid bilayers

Gabriela Québatte1, Eric Kitas2, Joachim Seelig1

  • 1Biozentrum, University of Basel, Div. of Biophysical Chemistry, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.

Biochimica Et Biophysica Acta
|November 5, 2013
PubMed

Insights

Retro-inverso-melittin lipid conjugates (riDOM) form stable nanoparticles that interact with lipid membranes. This peptide-lipid conjugate shows reduced membrane disruption and improved solubility, making it a promising candidate for applications requiring peptide-membrane interactions.

Area of Science:

  • Biophysics
  • Materials Science
  • Biochemistry

Background:

  • Melittin, a model peptide for membrane interactions, exhibits significant cytolytic and toxicological effects, limiting its use.
  • Retro-inverso-melittin (ri-melittin) offers a modified structure to overcome melittin's limitations.
  • Covalent linkage of ri-melittin to 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (riDOM) aims to improve its properties for membrane interactions.

Purpose of the Study:

  • To investigate the interaction of the novel lipid-peptide conjugate, riDOM, with phospholipid membranes.
  • To characterize the structural and thermodynamic properties of riDOM in aqueous and membrane environments.
  • To assess the potential of riDOM as a safer alternative to melittin for membrane applications.

Main Methods:

  • Circular dichroism (CD) spectroscopy to analyze secondary structure.
  • Dynamic light scattering and ζ-potential measurements for nanoparticle characterization.
  • High-sensitivity isothermal titration calorimetry (ITC) to determine binding thermodynamics.
  • (31)P NMR spectroscopy to study membrane structure changes.

Main Results:

  • riDOM forms stable, cationic nanoparticles (~13nm diameter) with good water solubility and high affinity for DNA and lipid membranes.
  • Upon membrane insertion, riDOM nanoparticles dissociate, forming transient pores with significantly reduced membrane leakiness compared to melittin.
  • riDOM insertion into membranes is entropy-driven, with half of its lipid hydrophobic surface involved in lipid-peptide interactions, ensuring dual solubility.
  • The β-structure of ri-melittin remains largely unchanged upon transfer to the membrane, while the lipid bilayer structure is preserved.

Conclusions:

  • riDOM represents a promising peptide-lipid conjugate with enhanced solubility and reduced toxicity compared to native melittin.
  • The unique packing of riDOM within lipid membranes facilitates its dual solubility and controlled membrane interaction.
  • riDOM's properties suggest potential applications in areas requiring safe and effective peptide-membrane interactions, such as drug delivery or biomaterials.
Keywords:
Cell penetrating peptideMelittinPeptide–membrane interactionPore formationThermodynamicTransfection

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