Investigation of the effects of polycations on Candida albicans membrane models and fungal cells. The effect of polymer structure and molecular weight.

Cationic polymers (polycations) represent a promising class of antimicrobial compounds whose physicochemical and biological properties can be tailored through appropriate structural design. The positive charge of these macromolecules indicates possible interactions with biological membranes. In this work, polycations differing in chemical structure (poly(2-(dimethylamino)ethyl methacrylate (PDMAEMA), poly(3-methacrylamido propyl trimethyl ammonium chloride) (PMAPTAC)) and molecular weight were investigated for their antifungal activity. The studies focused on the interactions of the polycations with model Candida albicans membranes that is the monolayers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and ergosterol. Model systems were employed to verify the mechanisms underlying polycation-membrane interactions. The antifungal activity of these compounds against various fungi was also tested. The results showed that the tested compounds exhibit different modes and strengths of interaction with ergosterol-containing membranes. Among the analyzed polymers, PDMAEMA exhibited significant effects on model systems causing changes in lipid packing and an increase in membrane fluidity, whereas PMAPTAC was less effective. Moreover, the polymer with a lower molecular weight modifies membrane properties more strongly compared to its higher-molecular-weight counterpart and additionally exhibits a greater affinity for membranes with a higher ergosterol content. PDMAEMA and PMAPTAC polymers exhibit selective antifungal activity against several opportunistic molds, particularly against Fusarium spp., Trichophyton spp., Candida parapsilosis, and Cryptococcus neoformans. The coexistence of selective antifungal activity and overall comparable antimycotic efficacy among the tested polymers highlights the prominent role of fungal cell properties in determining their susceptibility to polymers tested. Moreover, the selective toxicity of these compounds may be determined by the content of ergosterol in membranes.