Title:Structural Plasticity of EAK-16 Peptide Inducing Vesicle Membrane Leakage
Volume: 27
Issue: 8
Author(s): Abdul Majid *, Farah Naz and Muhammad Hassan Khaskheli
Affiliation:
- Department of Biochemistry, Shah Abdul Latif University, Khairpur,Pakistan
Keywords:
Ionic complementary peptide, peptide membrane interaction, membrane permeability, peptide folding, structurefunction
of peptide, zwitterionic lipid vesicles.
Abstract:
Background: Ionic complementary peptide EAK-16 has been studies for anticancer drug
delivery application. This is a 16 residues, short sequence peptide has ability to trosnform into
micro/nanoparticle via self-assembly. However, it is still not clear that how this can bind with cell
membrane to induce membrane leakage or delivering their cargo inside cell membrane.
Objective: The main objective of this work was to understand behaviour of secondary structure
conformation of peptide in solution and at lipid membrane interfaces and membrane permeability
of synthetic ionic complementary peptide EAK-16. The corresponding secondary structure
conformation was evaluated.
Methods: We performed biophysical investigation to probe the interaction of synthesised ionic
complementary peptide (EAK-16) with dimyristoylphospholcholine (DMPC) and
dimyristoylphosphoserine (DMPS) membrane interfaces. The folding behaviours of EAK-16 were
studied with Circular Dichroism (CD) spectroscopy. Membrane leakage with peptide was
confirmed with calcein leakage assay.
Results: Our finding of this study showed that in aqueous phase EAK-16 was predominantly folded
into β-sheets. The temperature could alter the β-sheets. However, in DMPC and DMPS membrane
interfaces, EAK-16 adopted helical conformation. EAK-16 has preference in perturbing anionic
compared Zwitterionic lipid vesicles. This study proposed that hydrophobic grooves of EAK-16
might be a key in the association with lipid bilayers. Secondly, a charge distribution of ionic
residues would also support the orientation at lipid bilayers. This peptide membrane association
would facilitate the membrane destabilisation.
Conclusion: This study demonstrated the supporting evidence that EAK-16 could interact with
lipid membranes and conforming to helical structure, while the helical conformation induced the
lipid membrane leakage. Overall, this study provides a physical rationale that ionic complementary
peptide can be a useful tool for designing and development of novel antibiotics and anticancer
agents along its previous drug delivery applications.
