Structural behaviour and gene delivery in complexes formed between DNA and arginine-containing peptide amphiphiles

Author(s)

Silva, Emerson R. ; Cooney, Gary ; Hamley, Ian W. ; Alves, Wendel A. ; Lee, Shannon ; O'Connor, Brendan F. ; Reza, Mehedi ; Ruokolainen, Janne ; Walls, Dermot

• Document type: Journal article
• Source: SOFT MATTER; v. 12, n. 45, p. 9158-9169, 2016.
• Web of Science Citations: 8

Abstract

We describe in depth the structure of complexes formed between DNA and two classes of arginine-containing peptide amphiphiles, namely, the lipopeptide PRW-C-16 (P = proline, R = arginine, W = tryptophan, C-16 = C-16 : 0 alkyl chain) and the bolaamphiphile RFL4FR (R = arginine, F = phenylalanine, L = leucine). A combination of X-ray and neutron scattering provided unprecedented insights into the local structure of these complexes. Lipopeptide-based complexes self-assembled into layered structures with large-scale fractal features, hosting DNA in the interstices. Bola-amphiphile scaffolds were characterized by planar structures with DNA strands presumably sandwiched in-between peptide nanotapes. Importantly, complexation did not affect the structural integrity of DNA in either of the two complexes. The bolaamphiphile conjugates displayed high levels of molecular ordering in contrast to the liquid-crystalline features observed in lipopeptide assemblies. Peptide-DNA complexes were assessed for their potential as a means to deliver the reporter vector pEGFP-N1 into SW480 human colon carcinoma cells. Successfully transfected cells expressed green fluorescent protein. The potentiating effect of PRW-C-16 on the cellular uptake of ectopic DNA was found to be much greater than that observed with RFL4FR. In contrast to the bolaamphiphile-based conjugate, the liquid-crystalline nature of the lipopeptide complex is likely to play a key role in DNA release and transfection efficiency since these weakly bound structures require lower energy expenditure during disassembly and load release. (AU)

• FAPESP's process: 15/24018-1 - Polymer-Peptide Conjugates for hydrogel formulation and its usage in detection
• Grantee: Wendel Andrade Alves
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/12674-6 - Structural investigations on model systems based on amphiphilic peptides
• Grantee: Emerson Rodrigo da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/03514-8 - Structural investigations on model-systems based on amphiphilic peptides
• Grantee: Emerson Rodrigo da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor