Decoding distinct membrane interactions of HIV-1 fusion inhibitors using a combined atomic force and fluorescence microscopy approach

摘要: Enfuvirtide and T-1249 are two potent HIV-1 fusion inhibitor peptides. Recent studies indicate that lipids play an important role in the mode of action those bioactive molecules. Using a combined tandem atomic force microscopy (AFM)-epifluorescence approach, we studied interaction both enfuvirtide with supported lipid bilayers. Fluid (ld)-gel (so) ld-liquid ordered (lo) phase-separated membrane systems were tested. Results, especially for T-1249, show significant activity at 15μM peptide concentration. opposition to enfuvirtide, induces increase surface roughness, decrease fluidity, bilayer thinning ld domains disruption so domain borders. In terms structural properties, possess distinct functional hydrophobic amphipathic HIV gp41. While only yields tryptophan-rich (TRD), possesses TRD pocket-binding (PBD). increases hydrophobicity while PBD enhances characteristics. As such, enhanced may be explained by synergism between its N-terminal segment hydrophophic C-terminal. Our findings provide valuable insights on molecular-level inhibitors, unraveling correlation their properties interactions as factor influencing antiviral activity. Ultimately, this work validates applicability AFM fluorescence approach evaluate mechanic bilayers upon membrane-active