Cation dependence of enniatin B/membrane-interactions assessed using surface-enhanced infrared absorption spectroscopy

27 February 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Enniatins are mycotoxins with well-known antibacterial, antifungal, antihelmintic and antiviral activity, which have recently come to attention as potential mitochondriotoxic anticancer agents. The cytotoxicity of enniatins is traced back to their ionophoric properties, in which the cyclodepsipeptidic structure results in enniatin:cation-complexes of various stoichiometries proposed as membrane-active species. In this work, we employed a combination of surface-enhanced infrared absorption (SEIRA) spectroscopy, tethered bilayer lipid membranes (tBLMs) and density functional theory (DFT)-based computational spectroscopy to monitor the cation-dependence (Mz+ = Na+, K+, Cs+, Li+, Mg2+, Ca2+) on the mechanism of enniatin B (EB) incorporation into membranes and identify the functionally relevant EBn:Mz+ complexes formed. We find that Na+ promotes a cooperative incorporation, modelled via an autocatalytic mechanism and mediated by a distorted 2:1-EB2:Na+ complex. K+ (and Cs+) leads to a direct but less efficient insertion into membranes due to the adoption of “ideal” EB2:K+ sandwich complexes. In contrast, the presence of Li+, Mg2+, and Ca2+ causes a (partial) extraction of EB from the membrane via the formation of “belted” 1:1-EB:Mz+ complexes, which screen the cationic charge less efficiently. Our results point to a relevance of the cation dependence for the transport into the malignant cells where the mitochondriotoxic anticancer activity is exerted.


bilayer lipid membrane
surface-enhanced infrared absorption spectroscopy

Supplementary materials

Supporting Information
Water background correction; EB incorporation SEIRA spectra in presence of Na+, K+, Cs+ and without any cation; Cation dependent reversibility in SEIRA spectra of EB; Kinetic model for EB membrane incorporation; SEIRA spectra during ion exchange


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.