Self-Assembled Multivalent (SAMul) Polyanion Binding-Impact of Hydrophobic Modifications in the Micellar Core on DNA and Heparin Binding at the Peripheral Cationic Ligands.
This paper reports a small family of cationic surfactants designed to bind polyanions such as DNA and heparin. Each molecule has the same hydrophilic cationic ligand and a hydrophobic aliphatic group with eighteen carbon atoms with one, two, or three alkene groups within the hydrophobic chain (C18-1, C18-2 and C18-3). Dynamic light scattering indicates that more alkenes lead to geometric distortion, giving rise to larger self-assembled multivalent (SAMul) nanostructures. Mallard Blue and Ethidium Bromide dye displacement assays demonstrate that heparin and DNA have markedly different binding preferences, with heparin binding most effectively to C18-1, and DNA to C18-3, even though the molecular structural differences of these SAMul systems are buried in the hydrophobic core. Multiscale modelling suggests that adaptive heparin maximises enthalpically favourable interactions with C18-1, while shape-persistent DNA forms a similar number of interactions with each ligand display, but with slightly less entropic cost for binding to C18-3-fundamental thermodynamic differences in SAMul binding of heparin or DNA. This study therefore provides unique insight into electrostatic molecular recognition between highly charged nanoscale surfaces in biologically relevant systems.
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
Buthaina
B
Albanyan
Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, 34127, Trieste, Italy.
Erik
E
Laurini
Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, 34127, Trieste, Italy.
Paola
P
Posocco
Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, 34127, Trieste, Italy.
Sabrina
S
Pricl
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
David K
http://orcid.org/0000-0002-9881-2714
DK
Smith
D001665:Binding Sites; D002412:Cations / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D000067493:Dynamic Light Scattering; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D056004:Molecular Dynamics Simulation; D049329:Nanostructures / Q000737:chemistry; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
D002412:Cations; D004247:DNA; D006493:Heparin; D008024:Ligands; D008823:Micelles; D000071228:Polyelectrolytes; D011108:Polymers
anion; electrostatics; molecular recognition; nanoscale; self-assembly