Characterizing the Interactions of Cell Membrane-Disrupting Peptides with Lipid-Functionalized Single-Walled Carbon Nanotube Systems for Antimicrobial Screening

Abstract

Lipid-functionalized single-walled carbon nanotubes (SWNTs) have garnered significant interest for their potential use in a wide range of biomedical applications. In this work, we used molecular dynamics simulations to study the equilibrium properties of SWNTs surrounded by the phosphatidylcholine (POPC) corona phase, and their interactions with three cell membrane disruptor peptides: colistin, TAT peptide, and crotamine-derived peptide. Our results show that SWNTs favor asymmetrical positioning within the POPC corona, so that one side of the SWNT, covered by the thinnest part of the corona, comes in contact with charged and polar functional groups of POPC and water. We also observed that colistin and TAT insert deeply into POPC corona, while crotamine-derived peptide only adsorbs to the corona surface. Compared to crotamine-derived peptide, colistin and TAT also induce larger perturbations in the thinnest region of the corona, by allowing more water molecules to directly contact the SWNT surface. In separate simulations, we show that three examined peptides exhibit similar insertion and adsorption behaviors when interacting with POPC bilayers, confirming that peptide-induced perturbations to POPC in conjugates and bilayers are similar in nature and magnitude. Furthermore, we observed correlations between the peptide-induced structural perturbations and the near-infrared emission of the lipid-functionalized SWNTs, which suggest that the optical signal of the conjugates transduces the morphological changes in the lipid corona. Overall, our findings indicate that lipid-functionalized SWNTs could serve as simplified cell membrane model systems for pre-screening of new antimicrobial compounds that disrupt cell membranes.

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

“…Computational studies revealed this corona to be akin to a membrane bilayer with the SWCNTs embedded in the lipid layer. 29 These sensors, now cloaked by a lipid corona, transduce membrane binding and disruption events as modulation of fluorescence intensity (Figure 1). This modulation likely results from changes to accessibility of the SWCNT surface to water, which behaves as a quenching agent.…”

“…Limitations of this approach include the unnatural membrane structure of the probes and the presence of nonreporting lipid vesicles. Unlike a true phospholipid bilayer found on cells, these lipids form a self-connected, curved monolayer around the nanotube that approximates a bilayer (see Yadav et al 29 for molecular dynamic simulated structures). These membranes are dense and large enough, relative to the nanotube, to capture some of the disruption behavior; however, there is likely less lipid mobility as well as a barrier to transverse interactions between the leaflets.…”

“…This supports recently published modeling work that gives insight into the molecular structure (curved monolayer around the nanoparticle that approximates a bilayer) and specificity of these probes. 29 As proof of concept, we first demonstrate that, when functionalized with phosphatidylcholine (PC) or lipopolysaccharides (LPS), SWCNTs respond to membrane disruption by fluorescence quenching. We then tested these sensors against different concentrations of…”

Predicting Serotonin Detection with DNA-Carbon Nanotube Sensors across Multiple Spectral Wavelengths

“…For all spectroscopy measurements, we excited our multichirality candidate nanosensors with a 721 nm laser. This laser wavelength predominately excites (10,2), (9,4), (8,6), (10,5), and (8,7) nanotube chiralities which predominately emit in the ca. 1100−1300 nm red-shifted range.…”