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    Engineered lipid bicelle nanostructures for membrane-disruptive antibacterial applications

    Year: 2021

    Journal: Appl. Mater. Today, Volume 22, MAR

    Authors: Sut, Tun Naw; Valle-Gonzalez, Elba R.; Yoon, Bo Kyeong; Park, Soohyun; Jackman, Joshua A.; Cho, Nam-Joon

    Organizations: National Research Foundation of Singapore through a Proof-of-Concept grant [NRF2015NRFPOC0001-19]; National Research Foundation of Korea (NRF) - Korean government (MSIT) [2020R1C1C1004385]; Korea Research Fellowship Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2019H1D3A1A01070318]; International Research & Development Program of the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2020K1A3A1A39112724]

    Keywords: Bicelle; Self-assembly; Nanostructure; Membrane disruption; Antibacterial

    Lipid bicelles are cell membrane-mimicking nanostructures that self-assemble from mixtures of long-and short-chain lipidic components and are widely used in various applications related to structural biology, drug delivery, and interfacial science. To date, most research efforts have focused on bicelles as passive structural carriers to host membrane proteins or hydrophobic drugs, while there remains untapped potential to engineer functionally active lipid bicelles that contain biologically important lipidic components for targeted applications. Herein, we developed antibiotic-free, antibacterial bicellar nanostructures composed of a long-chain phospholipid and glycerol monolaurate, which is a monoglyceride that exhibits membrane-disruptive inhibitory activity against various bacteria and membrane-enveloped viruses. Quartz crystal microbalance-dissipation and time-lapse fluorescence microscopy imaging experiments were conducted to identify fusogenic bicellar compositions with optimal levels of pore-like, membrane disruptive activity that was distinct from the activity of the monoglyceride alone. Cryogenic transmission electron microscopy was performed to characterize the lamellar-phase nanostructure properties of the lead bicelle composition along with in vitro antibacterial assays, which identified that the bicelles inhibited Staphylococcus aureus bacteria via a killing mechanism. Collectively, these findings demonstrate the potential of applying molecular-level engineering strategies to fabricate lipid bicelles with membrane disruptive properties relevant to anti-infective applications. (c) 2021 Elsevier Ltd. All rights reserved.
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