Kallmyer, N. E. | Search bioRxiv

bioRxiv2023

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

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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/525557v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@4c5645org.highwire.dtl.DTLVardef@1b3cd30org.highwire.dtl.DTLVardef@1643c6corg.highwire.dtl.DTLVardef@1bb096e_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Design and Validation of a Frugal, Automated, Solid-Phase Peptide Synthesizer

Solid phase peptide synthesis (SPPS) has enabled widespread use of synthetic peptides in applications ranging from pharmaceuticals to materials science. The demand for synthetic peptides has driven recent efforts to produce automated SPPS synthesizers which utilize fluid-handling components common to chemistry laboratories to drive costs down to several thousand dollars. Herein, we describe the design and validation of a more frugal SPPS synthesizer that uses inexpensive, consumer-grade fluid-handling components to achieve a prototype price point between US$300 and $600. We demonstrated functionality by preparing and characterizing peptides with a variety of distinct properties including binding functionality, nanoscale self-assembly, and oxidation-induced fluorescence. This system yielded micromoles of peptide at a cost of approximately $1/residue, a cost which may be further reduced by optimization and bulk purchasing.

biochemistry↗