Effect of the Alkyl Chain Length of Amphiphilic Ionic Liquids on the Structure and Dynamics of Model Lipid Membranes

Abstract

We compare the biophysical and structural aspects of the interaction of amphiphilic ionic liquids containing 1-alkyl-3-methylimidazolium cation ([C n MIM] + , n = 8, 12, or 16) with membranes composed of zwitterionic 1-palmitoyl-2-oleoyl-snglycero-3-phosphocholine (POPC) or anionic 1-palmitoyl-2-oleoyl-sn-glycero-3phospho-rac-glycerol (POPG). Liposome affinity and permeabilization were determined using ζ-potential and fluorescence studies, correlated with the cytoxicity of [C n MIM] + Br − toward HeLa cell lines. Membrane affinity is strongest in the case of [C 16 MIM] + Br − followed by [C 12 MIM] + Br − and [C 8 MIM] + Br − for both membranes, and trends remained the same in the case of membrane permeability and cytotoxicity. Solid-state NMR spectroscopy was used to localize [C n MIM] + inside the lipid bilayers and to study their impact on the head group and acyl chain structures and dynamics of the lipid molecules. The charged ring moiety of the [C n MIM] + is localized in the lipid−water interface of the membranes irrespective of the chain length and membrane surface charge. While [C 8 MIM] + binds the membrane most weakly, it induces the largest disorder in the lipid chain region. A lack of fast flip-flop motions of the amphiphiles in the case of long chain [C 16 MIM] + is suggested to render the membrane unstable, which increases its permeability. Between the lipid molecules, the POPC membrane incurs larger disorder in lipid chain packing upon insertion of [C n MIM] + molecules. The study provides structural details of the impact of increasing chain lengths in [C n MIM] + on the structural properties of lipid bilayers.

Amphiphilic ionic liquid induced fusion of phospholipid liposomes

“…14 Cytotoxicity of ionic liquids is rooted in the amphiphilic nature of cations, and is known to correlate directly with length of alkyl chains. 15 Various computational studies, [16][17][18] and investigations based on neutron reflectometry [19][20] and solid-state NMR 15,21 have revealed the structural details of their interaction with lipid bilayers. In this mechanism, the alkyl chain enters the hydrophobic phase (OL of bilayer) while the charged head group resides at the lipid-water interface.…”

“…In this mechanism, the alkyl chain enters the hydrophobic phase (OL of bilayer) while the charged head group resides at the lipid-water interface. 15,[19][20][21] Insertion of cations in this manner puts the OL under strain ultimately leading to membrane permeabilization and disruption. 22 A similar mechanism could also lead to fusion of vesicles.…”

“…From the fast component of quench kinetics, the percentage ( ) of NBD molecules in the IL was found to be 45% (in POPC) and 60% (in POPG). %Hemifusion was then calculated by using the difference between the expected IL mixing in the event of full fusion ( ) and the observed IL mixing asRESULTS AND DISCUSSIONSImidazolium based ionic liquids are known for their ability to permeabilize the lipid bilayers 15,21,33. This is mainly studied by observing the fraction of trapped dye leaking out of LUVs as a function of time.…”

Amphiphilic Ionic Liquid Induced Fusion of Phospholipid Liposomes

“…A comparison between POPC and POPG tells us that LUVs of former require lower [C 12 MIM] + Brconcentrations to fuse. This is counter-intuitive from an electrostatic point of view since [C 12 MIM] + bound POPC LUVs possess a net positive surface charge and hence should be less However, insertion of [C 12 MIM] + molecules renders POPC bilayers more disordered (<S>=0.127) as compared to POPG (<S>=0.154),15 a factor which could assist membrane fusion through surface exposure of hydrophobic tails thus overcoming the hydration barrier 40. Some membrane fusion models have suggested that formation of an initial contact between merging bilayers known as prestalkmembrane 37,[41][42].…”

“…Even at 1 mM, where no [C 12 MIM] + Brinduced fusion is expected, one observes 6% and 2% total lipid mixing in POPC and POPG LUVs, respectively. The observed difference is probably due to the fact that more [C 12 MIM] + molecules bind POPC (K= 590 ± 60 mM -1 ) as compared to POPG (K= 340 ± 30 mM -1 ) membranes 15. In a probe dilution assay, this value will depend on the lateral diffusion of lipids in a bilayer which once again highlights themore dynamic nature of POPC bilayers in presence of [C 12 MIM] + .…”