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

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

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

17 Citations (Scopus)

Abstract

We describe in depth the structure of complexes formed between DNA and two classes of arginine-containing peptide amphiphiles, namely, the lipopeptide PRW-C16 (P = proline, R = arginine, W = tryptophan, C16 = C16:0 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-C16 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.

Original languageEnglish
Pages (from-to)9158-9169
Number of pages12
JournalSoft Matter
Volume12
Issue number45
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

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