Lipid-Functionalized Single-Walled Carbon Nanotubes as Probes for Screening Cell Wall Disruptors

Area of Science:

• Biomaterials Science
• Nanotechnology
• Analytical Chemistry

Background:

• Membrane-active molecules are crucial for drug delivery and antimicrobials.
• Current testing methods for these molecules face limitations in throughput, cost, and modularity, especially when using pathogenic cells.
• Existing model systems have intrinsic limitations for accurate testing.

Purpose of the Study:

• To develop a novel abiotic sensor for detecting membrane interactions.
• To provide a high-throughput, cost-effective, and modular alternative to current testing methods.
• To enable the evaluation of drug selectivity and interaction mechanisms with membranes.

Main Methods:

• Utilized semiconducting single-walled carbon nanotubes (SWCNTs) as near-infrared fluorescent transducers.
• Created an abiotic sensor by suspending SWCNTs in lipid to form a bilayer corona.
• Monitored changes in SWCNT fluorescence, correlating signal modulation (brightening/attenuation) with membrane binding and disruption.

Main Results:

• Demonstrated sensor response to chemical agents (ethanol, SDS) and physical disruption (electrical pulses).
• Successfully deconvoluted interaction mechanisms of cell-penetrating and antimicrobial peptides.
• Assessed antimicrobial drug selectivity by functionalizing SWCNTs with different bacterial lipopolysaccharides (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli).

Conclusions:

• The SWCNT-based abiotic sensor effectively reports membrane interactions and disruptions.
• This sensor system offers a versatile platform for evaluating membrane-active molecules, including antimicrobials.
• The developed method allows for high-throughput screening and assessment of drug selectivity against specific bacterial membranes.