Interaction of choline salts with artificial biological membranes: DSC studies elucidating cellular interactions

Abstract

To better understand the relationship between the relative cytotoxicity of diluted ionic liquids and their specific interaction with biological membranes, the thermotropic behavior of model lipid membrane systems formulated in a series of choline based organic salts was investigated. Unilamellar vesicles prepared from dipalmitoylphosphatidylcholine (DPPC) were exposed to a series of choline phosphate salts at a concentration of 10 mM at pH 7.40, and the gel to liquid-crystalline state transition was examined using differential scanning calorimetry. The choline salts that were observed to have a low relative toxicity in previous studies induced minimal changes in the lipid phase transition behavior of these model membranes. In contrast, the salts choline bis(2,4,4-trimethylpentyl)phosphinate (CTMP) and choline bis(2-ethylhexyl)phosphate (CBEH), both of which were observed to have high relative toxicity, caused distinct disruptions in the lipid phase transition behavior, consistent with penetration of the salts into the acyl chains of the phospholipids. CTMP reduced the Tm and enthalpy of the main transition of DPPC while CBEH induced the equilibration of alternate phases.

Effect of choline carboxylate ionic liquids on biological membranes

“…DPPC membranes were exposed to choline carboxylate compounds with m = 2–10 and oleate in order to identify trends in lipid bilayer interactions [22]. As shown in Fig.…”

“…Large, unilamellar vesicles of DPPC were prepared by extrusion as described by Weaver et al [22], using membranes with a pore size of ≤0.2 μm. Briefly, lyophilized DPPC powder was hydrated with 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer at pH 7.40, and 70°C, then incubated for 30 min.…”

Room-temperature ionic liquids meet bio-membranes: the state-of-the-art

“…Figure reproduced with permission from the publisher upon the absorption of RTIL cations, and (iv) Importance of the chemistry of the molecules (Weaver et al 2013;Gal et al 2012;Lee et al 2015). The effects of RTILs on the thermotropic behavior of biomembranes were also probed in several reports (Weaver et al 2013;Wang et al 2016;Jeong et al 2012. ) At low concentrations of RTILs, the variation of the main phase transition of phospholipids bilayers is negligible, and at high concentration the variation is of the order of 5 to 10 degrees, sometimes reaching 20 degrees, but this just before the collapse of the bilayers.…”

“…(Yoo et al 2016b) suggest that it is the inability of some RTILs to diffuse from the outer leaflet to the inner leaflet of the phospholipid bilayer which is at the origin of the bilayer disruption. Figure reproduced with permission from the publisher upon the absorption of RTIL cations, and (iv) Importance of the chemistry of the molecules (Weaver et al 2013;Gal et al 2012;Lee et al 2015). The effects of RTILs on the thermotropic behavior of biomembranes were also probed in several reports (Weaver et al 2013;Wang et al 2016;Jeong et al 2012.…”

The partition and transport behavior of cytotoxic ionic liquids (ILs) through the DPPC bilayer: Insights from molecular dynamics simulation

“…For example, a direct relationship between the alkyl sidechain length of alkylimidazolium salts and cellular toxicity has been found (Stolte et al, 2006). Furthermore, some experimental studies have been conducted to determine the toxicity of choline-based ILs (Weaver et al, 2013). The results revealed a range of toxicities from low (choline dihydrogen phosphate (CDHP)) to high (choline bis (2,4,4-trimethylpentyl) phosphinate (CTMP) and choline bis (2-ethylhexyl) phosphate (CBEH)) based on the anion effect ratio (Stolte et al, 2006;Weaver et al, 2010).…”