Effect of tetracycline antibiotic on the monolayers of phosphatidylcholines at the air–water interface

•Tetracycline interacts with phosphatidylcholine monolayers through electrostatic interactions.•Contact potential difference experiments point to the oriented adsorption at/in the head group region of phospholipid monolayer.•Tetracycline induces disorder in the hydrophobic part, particularly visible in DMPC monolayer.•Brewster angle experiments show polymorphic changes in the monolayers.

Tetracycline is a broad-spectrum antibiotic belonging to the polyketide class. It is widely used against bacterial infections as well as food additive to a live-stock. Since tetracycline is resistant against degradation, it accumulates in the environment, leading also to antibiotic residues in animal and food products, which is now considered to be an important health risk because of increasing antibiotic resistance of pathogenic microorganisms. In this work we studied the interactions of tetracycline with phospholipid monolayers at the air/water interface in order to elucidate the mechanism of its action on cell membrane biomimetic system. We selected three phosphatidylcholines, having the same head-group structure, differing with respect to their hydrophobic chain length, the presence of unsaturated bonds between carbon atoms and, consequently, the phase transition temperature. Analysis of the results presented here suggests that tetracycline interacts with the three phosphatidylcholines mainly through the electrostatic interactions with hydrophilic groups of these lipids. On the other hand, the shape of presented pressure-area isotherms and their compressibility moduli show the synergistic effect of hydrophobic interactions that are larger for longer alkyl chains, promoting easier ordering of monolayer molecules with increased surface pressure when drug is present in the subphase, particularly for saturated DPPC. Based on our contact potential data we think that positively charged tertiary amino group of TC is facing negatively charged phosphate groups of phosphatidylcholines, penetrating only the hydrophilic head group region but not the hydrophobic moiety of these monolayers. However, the observed differences in CPD values for the case of DMPC point toward the drug disordering influence also on the organization of the hydrophobic region of this monolayer. This is because the drug penetration disturbs the van der Waals ordering interactions between its shorter hydrophobic chains to a greater extent comparing to DPPC and DOPC molecules.

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