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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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Molecular Dynamics Reveal Key Steps in BAR-Related Membrane Remodeling
Endocytosis plays a complex role in pathogen-host interactions. It serves as a pathway for pathogens to enter the host cell and acts as a part of the immune defense mechanism. Endocytosis involves the formation of lipid membrane vesicles and the reshaping of the cell membrane, a task predominantly managed by proteins containing BAR (Bin1/Amphiphysin/yeast RVS167) domains. Insights into how BAR domains can remodel and reshape cell membranes provide crucial information on infections and can aid the development of treatment. Aiming at deciphering the roles of the BAR dimers in lipid membrane bending and remodeling, we conducted extensive all-atom molecular dynamics simulations and discovered that the presence of helix kinks divides the BAR monomer into two segments—the “arm segment” and the “core segment”—which exhibit distinct movement patterns. Contrary to the prior hypothesis of BAR domains working as a rigid scaffold, we found that it functions in an “Arms-Hands” mode. These findings enhance the understanding of endocytosis, potentially advancing research on pathogen-host interactions and aiding in the identification of new treatment strategies targeting BAR domains.
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- Award ID(s):
- 2237369
- PAR ID:
- 10627961
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Pathogens
- Volume:
- 13
- Issue:
- 10
- ISSN:
- 2076-0817
- Page Range / eLocation ID:
- 902
- 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/10.3390/pathogens13100902
