Complexes of Cationic Pyridylphenylene Dendrimers with Anionic Liposomes: The Role of Dendrimer Composition in Membrane Structural Changes

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2225
• Main Authors: Efimova, Anna A, Sorokina, Svetlana A, Trosheva, Kseniya S, Yaroslavov, Alexander A, Shifrina, Zinaida B
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.01.2023; MDPI
• Subjects: Adsorption; biomembrane; Cations; Cell membranes; Cholesterol; complex; dendrimer; Dendrimers; Dendrimers - chemistry; Electrostatic properties; Fluorescence spectroscopy; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Investigations; Light scattering; lipid bilayer; Lipid bilayers; Lipid Bilayers - chemistry; Lipid membranes; Lipids; liposome; Liposomes; Liposomes - chemistry; migration; Particle size; Photon correlation spectroscopy; Polymers; Rigid structures; Sodium chloride; Static Electricity; migration; lipid bilayer; biomembrane; liposome; complex; dendrimer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032225

In the last decades, dendrimers have received attention in biomedicine that requires detailed study on the mechanism of their interaction with cell membranes. In this article, we report on the role of dendrimer structure in their interaction with liposomes. Here, the interactions between cationic pyridylphenylene dendrimers of the first, second, and third generations with mixed or completely charged pyridyl periphery (D , D , D , and D ) with cholesterol-containing (CL/Chol/DOPC) anionic liposomes were investigated by microelectrophoresis, dynamic light scattering, fluorescence spectroscopy, and conductometry. It was found that the architecture of the dendrimer, namely the generation, the amount of charged pyridynium groups, the hydrophobic phenylene units, and the rigidity of the spatial structure, determined the special features of the dendrimer-liposome interactions. The binding of D and D with almost fully charged peripheries to liposomes was due to electrostatic forces: the dendrimer molecules could be removed from the liposomal surfaces by NaCl addition. D and D did not display a disruptive effect toward membranes, did not penetrate into the hydrophobic lipid bilayer, and were able to migrate between liposomes. For D , a dendrimer with a mixed periphery, hydrophobic interactions of phenylene units with the hydrocarbon tails of lipids were observed, along with electrostatic complexation with liposomes. As a result, defects were formed in the bilayer, which led to irreversible interactions with lipid membranes wherein there was no migration of D between liposomes. A first-generation dendrimer, D , which was characterized by small size, a high degree of hydrophobicity, and a rigid structure, when interacting with liposomes caused significant destruction of liposomal membranes. Evidently, this interaction was irreversible: the addition of salt did not lead to the dissociation of the complex.