Membrane-penetrating proteins play a key role in defense against foreign or competing microbes and have been used to design vehicles that can deliver therapeutics or combat antibiotic-resistant pathogens. The study of these naturally occurring proteins has led to the design of new, synthetic cell-penetrating peptides. These designer peptides have been used to deliver large molecules, such as GFP, into the cytoplasm and to lyse notoriously drug-resistant bacteria, such as S. aureus and P. aeruginosa. While these peptides demonstrate great potential, screening techniques to find and optimize their sequences are limited by the timescale of cell growth and require stringent safety protocols to prevent exposure of personnel to target pathogens. Herein, we demonstrate fluorescent single-walled carbon nanotube (SWNT) sensors as abiotic cell proxies to test penetrating peptides. These proxies are constructed by suspending SWNT in either phosphatidylcholine (PC) or lipopolysaccharide (LPS) to simulate the outer surface of an animal cell or Gram-negative bacterium respectively. Disruptions to this simulated cell surface, whether caused by surfactants, chaotropes, electrical potential gradients, or temperature changes, expose the SWNT surface to solvent and cause an immediate quenching of the fluorescent signal. When screening cell-penetrating peptides with these proxies, concentration thresholds are observed; below these thresholds, cell-penetrating peptides cause an increase to fluorescent signal (binding of the peptide to the SWNT membrane proxy), and above these thresholds, peptides cause a rapid decrease to signal (penetration of membrane proxy). The magnitude of the signal drop of PC-SWNT correlated inversely with the activation energy of peptide translocation. The observed concentration threshold similarly correlated inversely with published uptake efficiencies. A short response time (&lt; 30 s) and reduced risk of pathogen exposure make this sensor a potentially valuable pre-screening tool for cell penetrating and antimicrobial peptide discovery and design.

Lipid-functionalized single-walled carbon nanotubes as abiotic cell proxies to screen membrane-penetrating peptides for use in drug delivery and antimicrobials development

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.