Fiche publication
Date publication
août 2025
Journal
Biochimica et biophysica acta. Biomembranes
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
Tous les auteurs :
De K, Bryder K, Aisenbrey C, Mörgelin M, Bechinger B
Lien Pubmed
Résumé
Collagen VI is an extracellular matrix protein forming complex microfibrillar networks in connective tissues. Specifically, we focused on its role in innate immunity, in particular on cationic sequence motifs from the α3(VI)-chain, which exhibit strong antibacterial properties against both Gram-positive and Gram-negative bacteria in vitro and in vivo. Cytotoxicity assays revealed minimal to no adverse effects, even at concentrations effective against bacterial pathogens. This favorable safety profile suggests that these antimicrobial peptides selectively target bacterial membranes while sparing host cells, making them promising candidates for therapeutic development. The membrane structure and interactions of two antimicrobial peptides were investigated in quantitative detail using solid-state NMR, CD and fluorescence spectroscopies. Whereas calcein release was somewhat more pronounced from POPE/POPG 3/1 vesicles when compared to POPC/30 % cholesterol, this activity is about two orders of magnitude increased when POPC/POPG 3/1 liposomes are investigated. This pronounced lipid dependence was reproduced with magainin 2, a well-known linear cationic AMP. In lipid titration experiments both collagen-derived peptides showed a transition from predominantly random coil to helical conformations. Quantitative evaluation of membrane association required the presence of PEG-lipids which are known to prevent the agglutination of POPE/POPG 3/1 liposomes. A dissociation constant in the 260 μM range was observed for GVR28 while the binding isotherms reveal an intermediate state when SFV33 associates with bacterial membranes. H solid-state NMR reveals considerable membrane disorder of the deuterated PG palmitoyl chain in POPE/POPG membranes. The ensemble of biophysical data suggests two distinct modes of action for the collagen derived peptides.
Mots clés
Antimicrobial peptide, Collagen VI, Cytotoxicity, Extracellular matrix, Innate immunity, Magainin, Mode of action, Peptide-lipid interactions, Soft tissue infection, Surface coating
Référence
Biochim Biophys Acta Biomembr. 2025 08 28;:184448
