Phospholipid Composition Modulates Carbon Nanodiamond-Induced Alterations in Phospholipid Domain Formation

Abstract

The focus of this work is to elucidate how phospholipid composition can modulate lipid nanoparticle interactions in phospholipid monolayer systems. We report on alterations in lipid domain formation induced by anionically engineered carbon nanodiamonds (ECNs) as a function of lipid headgroup charge and alkyl chain saturation. Using surface pressure vs area isotherms, monolayer compressibility, and fluorescence microscopy, we found that anionic ECNs induced domain shape alterations in zwitterionic phosphatidylcholine lipids, irrespective of the lipid alkyl chain saturation, even when the surface pressure vs area isotherms did not show any significant changes. Bean-shaped structures characteristic of dipalmitoylphosphatidylcholine (DPPC) were converted to multilobed, fractal, or spiral domains as a result of exposure to ECNs, indicating that ECNs lower the line tension between domains in the case of zwitterionic lipids. For membrane systems containing anionic phospholipids, ECN-induced changes in domain packing were related to the electrostatic interactions between the anionic ECNs and the anionic lipid headgroups, even when zwitterionic lipids are present in excess. By comparing the measured size distributions with our recently developed theory derived by minimizing the free energy associated with the domain energy and mixing entropy, we found that the change in line tension induced by anionic ECNs is dominated by the charge in the condensed lipid domains. Atomic force microscopy images of the transferred anionic films confirm that the location of the anionic ECNs in the lipid monolayers is also modulated by the charge on the condensed lipid domains. Because biological membranes such as lung surfactants contain both saturated and unsaturated phospholipids with different lipid headgroup charges, our results suggest that when studying potential adverse effects of nanoparticles on biological systems the role of lipid compositions cannot be neglected.

Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution

“…Anionic diamond NPs can alter the packing and shape of ordered gel domains. 20 Positively-charged dendrimers and polymeric NPs have been shown to selectively disrupt the liquid phase of the bilayer over the gel phase. 21,22 Amphiphilic dendrimers have been shown to interact distinctly with bilayers of different phasesinducing partial solubilization of fluid bilayers, lipid patches and local depressions in gel bilayers, and a ribbon-like network with spherical aggregates in bilayers with both fluid and gel phases.…”

“…21,22,25 Fluorescence microscopy has also been used to examine interactions between NPs and phase-segregated model membranes. 20,24,27 While not attaining the resolution of AFM, fluorescence microscopy provides high detection selectivity enabled by fluorescence tagging. 28 Correlative AFM and fluorescence microscopy can localize NPs in relation to other fluorescently tagged biomolecules with very high spatial resolution and detection selectivity.…”

Combined effect of synthetic protein, Mini-B, and cholesterol on a model lung surfactant mixture at the air–water interface

“…Further, some of us have also previously shown that SP-B causes an increase in the line tension of a clinical lung surfactant, an important biophysical property of phospholipid films at the air–water interface, which can control the overall energy of the lipid films [29]. By correlating high resolution atomic force microscopy (AFM) images to calculations of line tension changes in different binary lipid films, we have also recently shown that a change in line energy can be directly related to the tendency of a molecule to act as a line active species [31]. Further, previous research by McConnel and co-workers has established the line tension lowering ability of cholesterol [32].…”

Impact of Engineered Carbon Nanodiamonds on the Collapse Mechanism of Model Lung Surfactant Monolayers at the Air-Water Interface

“…Thus, in addition to the surface pressure-area isotherms, the surface morphology should be carefully studied while assessing the behavior of the nanoparticles. Similarly, previous work from our lab has shown that the actual composition of the lipid mixture used can also lead to differences in interactions with nanoparticles [22]. However, the impact of nanoparticles on collapse mechanism in phospholipid monolayers is currently not well understood and has not been studied in detail.…”

“…Studies have shown that the chemistry of the surfactant mixtures (phospholipid combinations and presence of LS proteins or their synthetic analogs) enable fold formation during compression and reincorporation of material during expansion cycles [23][24][25]. On the other hand, our previous work, focused on ECN induced changes in lipid domain packing in the LE-LC regions has shown that differences in lipid-ECN interactions are modulated by other lipid headgroup charge and tail saturation [22]. Specifically, we observed that at lower surface pressures, the anionic ECNs behave as line active species when interacting with zwitterionic phospholipids.…”