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Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point. However, plasma membranes are also asymmetric in terms of lipid type, lipid abundance, leaflet tension, and corresponding cholesterol distribution, suggesting that rafts cannot be examined separately from questions about elasticity, curvature torques, and internal mechanical stresses. Unfortunately, it is challenging to capture this wide range of physical phenomenology in a single model that can access sufficiently long length- and time scales. Here we extend the highly coarse-grained Cooke model for lipids, which has been extensively characterized on the curvature-elastic front, to also represent raft-like lo/ld mixing thermodynamics. In particular, we capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. We furthermore examine elasticity and lipid diffusion for both phase separated and pure systems and how they change upon the addition of cholesterol. We anticipate that this model will enable significant insight into lo/ld phase separation and the associated question of lipid rafts for membranes that have compositionally distinct leaflets that are likely under differential stress—like the plasma membrane.
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Preferential interactions of primary amine-terminated quantum dots with membrane domain boundaries and lipid rafts revealed with nanometer resolution
The initial interactions of engineered nanoparticles (NPs) with living cells are governed by physicochemical properties of the NP and the molecular composition and structure of the cell membrane. Eukaryotic cell membranes contain lipid rafts – liquid-ordered nanodomains involved in membrane trafficking and molecular signaling. However, the impact of these membrane structures on cellular interactions of NPs remains unclear. Here we investigate the role of membrane domains in the interactions of primary amine-terminated quantum dots (Qdots) with liquid-ordered domains or lipid rafts in model membranes and intact cells, respectively. Using correlative atomic force and fluorescence microscopy, we found that the Qdots preferentially localized to boundaries between liquid-ordered and liquid-disordered phases in supported bilayers. The Qdots also induced holes at these phase boundaries. Using super resolution fluorescence microscopy (STORM), we found that the Qdots preferentially co-localized with lipid rafts in the membrane of intact trout gill epithelial cells – a model cell type for environmental exposures. Our observations uncovered preferential interactions of amine-terminated Qdots with liquid-ordered domains and their boundaries, possibly due to membrane curvature at phase boundaries creating energetically favorable sites for NP interactions. The preferential interaction of the Qdots with lipid rafts supports their potential internalization via lipid raft-mediated endocytosis and interactions with raft-resident signaling molecules.
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- Award ID(s):
- 1503408
- PAR ID:
- 10146111
- Date Published:
- Journal Name:
- Environmental Science: Nano
- Volume:
- 7
- Issue:
- 1
- ISSN:
- 2051-8153
- Page Range / eLocation ID:
- 149 to 161
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C9EN00996E
