Micellization of Lipopeptides Containing Toll-like Receptor Agonist and Integrin Binding Sequences
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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Date
2024-12-18
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Mcode
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en
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11
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ACS Applied Materials and Interfaces, Volume 16, issue 50, pp. 68713-68723
Abstract
Short bioactive peptide sequences are of great interest in biomaterials development. We investigate the self-assembly of a lipopeptide containing both the highly cationic CSK4 toll-like receptor agonist hexapeptide sequence and RGDS integrin-binding motif, i.e., C16-CSK4RGDS, as well as the control containing a scrambled terminal sequence C16-CSK4GRDS. Both lipopeptides are found to form micelles, as revealed by small-angle X-ray scattering and cryogenic transmission electron microscopy, and modeled using atomistic molecular dynamics simulations. We carefully examined methods to probe the aggregation of the molecules, i.e. to obtain the critical micelle concentration (CMC). Fluorescent probe assays using 1-anilino-8-naphthalenesulfonate (ANS) reveal low CMC values, 1-2 μM, which contrast with consistent values more than 2 orders of magnitude larger obtained from surface tension and electrical conductivity as well as unexpected UV/vis absorption spectra discontinuities and fluoresccence probe assays using Nile red. The anomalous results obtained from an ANS fluorescence probe are ascribed to the effect of ANS binding to the cationic (lysine and arginine) residues in the lipopeptide, which leads to a conformational change, as shown by circular dichroism, even at low concentrations below the actual CMC. Despite the small change in the peptide sequence (swapping of G and R residues), there is surprisingly a significant difference in the aggregation propensity and association number, both of which are greater for C16-CSK4GRDS. Both lipopeptides are cytocompatible (with fibroblasts and myoblasts) at low concentration, although cytotoxicity is noted at higher concentration.Description
Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.
Keywords
aggregation, biosurfactants, cytocompatibility, lipopeptides, micelles, molecular dynamics
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Citation
Castelletto, V, de Mello, L R, Seitsonen, J & Hamley, I W 2024, ' Micellization of Lipopeptides Containing Toll-like Receptor Agonist and Integrin Binding Sequences ', ACS Applied Materials and Interfaces, vol. 16, no. 50, pp. 68713-68723 . https://doi.org/10.1021/acsami.4c18165