Morphology-Induced Defects Enhance Lipid Transfer Rates

Abstract

Molecular transfer between nanoparticles has been considered to have important implications regarding nanoparticle stability. Recently, the interparticle spontaneous lipid transfer rate constant for discoidal bicelles was found to be very different from spherical, unilamellar vesicles (ULVs). Here, we investigate the mechanism responsible for this discrepancy. Analysis of the data indicates that lipid transfer is entropically favorable, but enthalpically unfavorable with an activation energy that is independent of bicelle size and long- to short-chain lipid molar ratio. Moreover, molecular dynamics simulations reveal a lower lipid dissociation energy cost in the vicinity of interfaces ("defects") induced by the segregation of the long- and short-chain lipids in bicelles; these defects are not present in ULVs. Taken together, these results suggest that the enhanced lipid transfer observed in bicelles arises from interfacial defects as a result of the hydrophobic mismatch between the long- and short-chain lipid species. Finally, the observed lipid transfer rate is found to be independent of nanoparticle stability.

Aggregation‐Enhanced Photoluminescence and Photoacoustics of Atomically Precise Gold Nanoclusters in Lipid Nanodiscs (NANO2)

“…The total bilayer thickness (t core + 2t axial , ≈5.5-5.8 nm) is practically invariant, the drastic increase of t rim (from 1.4 nm to 6.0 nm) and increased ρ rim (from 9.72 × 10 −6 to 10.1 × 10 −6 Å −2 ) in NANO 2 compared to the pristine bicelles suggest that at the low Au-C16:lipid ratio of 1:500 most of the entrapped Au-C16 is preferably localized near the disc rim. This can be explained by the fact that disc rim, which is mainly composed of short-chain DHPC, has a large spontaneous curvature and is more fluidic, [18] thereby making it possible to accommodate higher-curvature objects like AuNCs (Figure 3c), consistent with previous MD simulations, [19] and further enhancing ER. Note that the best fits to the SAXS data of all NANO 2 , whose AuNCs were conjugated with different ligand lengths (from C4 to C16), revealed discoidal morphology at the same AuNC-to-lipid ratio of 1:500 ( Figure S7, Supporting Information).…”

“…These materials have to perform multiple functions and satisfy numerous requirements, starting from simplicity and reproducibility of preparation to robust imaging and solid performance in cells. Here, we report the development and properties of a novel nano-in-nano (NANO 2 ) platform through trapping thiolate-protected gold nanoclusters (AuNCs), such as Au 25 (SC 16 H 33 ) 18 (Au-C16), [1] in a welldefined lipid-based nanodisc. [2] NANO 2 spontaneously forms via hydrophobic interactions between the lipid tails and the linear thiolated ligands, which protect the gold core, and is a potential candidate for theranostic nanocarrier due to…”

Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes

“…A higher curvature in bicelles as compared to liposomes can explain why the kinetics of lipid exchange was 2–3 orders of magnitude faster in bicelles than in liposomes 41 . Indeed, higher curvatures imply a higher hydrophobic mismatch between the different lipids species close to the edge for bicelles and by the rim of the ApoA1 protein in nanodiscs where the bilayer patch becomes less dense and well-defined 44,46 .…”

“…It should be noted that the main lipids in these lipoprotein samples are unsaturated species. Up until now, most lipid exchange studies have used synthetic saturated lipids and have shown that differences in acyl chain length determine the exchange rates; however, the effect of unsaturation is yet to be explored 41–44,46 . The present study follows the exchange between human lipoproteins and membranes composed of natural lipids carrying long, unsaturated fatty acids.…”

Measuring Lipid Transfer Protein Activity Using Bicelle-Dilution Model Membranes

“…Bicelles and lipoprotein nanodiscs at high concentrations have been used previously as donor and acceptor model membranes to show spontaneous lipid transfer that is fast, nonspecific, and likely occurs via a collisional-based mechanism . Interestingly, fast spontaneous lipid transfer via collisions among polymer-bounded nanodiscs has also recently been reported in agreement with transfer mechanisms reported for bilayer vesicles at high concentrations over three decades ago. , Lowering the lipid model membrane concentrations or adding small amounts of charged lipid mitigates the model membrane collisional contacts and vastly reduces the rate of nonspecific spontaneous lipid transfer. , In recent studies of DMPC/DHPC or DPPC/DHPC bicelles containing 5 mol % of negatively charged phosphatidylglycerol, , the spontaneous transfer rates for the DMPC or DPPC bicelle bilayer-matrix lipid were slow and with their half-times differing from several hours to hundreds of hours, respectively, in agreement with earlier bilayer vesicles studies. The findings suggest a solubility-driven exchange via lipid monomer transfer through the aqueous medium, in agreement with studies of conventional bilayer vesicles , and lipoprotein nanodiscs …”