Enniatins have been reported to show specific enzyme inhibiting and mitochondriotoxic properties, which are relevant to their anticancer activity as well as to potential human and animal health issues. A prerequisite for such functions of enniatins is the entry into the cell such that the specific targets can be reached. Na + and K + are main cations in the extracellular medium and our experiments support that their presence assists the incorporation into the membrane (Figure and summary in Figure ). Ion exchange experiments using the mono-valent Na + , K + and Cs + allowed detecting the proposed EBn:M + species, which were adopted reversibly (Figure , Figure ), suggesting this as a common behavior of EB with alkaline cations (except for Li + ). Instead, we note that Li + , Mg 2+ , and Ca 2+ demonstrated irreversible behavior, in which EB was extracted from the membrane judging by the overall SEIRA intensities (Figure , Figure ). As such, overall bivalent cations could play a relevant role of abstracting EB from the membrane and thus facilitating the transfer into the intracellular medium. The observation that Li + stands as the exception to these can be rationalized based on the diagonal relationship between Li + and Mg 2+ due their similar charge densities of 100 -120 C mm -3 . Despite the much lower physiological concentrations of Mg 2+ and Ca 2+ it is again noteworthy that both ions (together with Na + and Li + , but not K + ) are enriched within the membrane headgroup region, providing direct access to efficiently bind EB. If membrane extraction is mediated by EB complexes with Mg 2+ and Ca 2+ (and Li + ), the belted 1:1 EB:M z+ in complex is a likely candidate in this process as it provide a minimal charge screening for the cations.