Antimicrobial Polymers at the Membrane Interface: Impact of Macromolecular Architecture

Antimicrobial resistance (AMR) is a major cause of death worldwide. This urges the search for alternatives to antibiotics, and antimicrobial polymers hold promise due to their reduced susceptibility to AMR. The topology of such macromolecules has a strong impact on their activity, with bottlebrush architectures outperforming their linear counterparts significantly. Consequently, understanding the specific behavior of macromolecules featuring a confined conformation of linear subunits is pertinent. This study focusses on revealing fundamental differences between architectures regarding properties as well as interaction with biological membranes. Various analytical techniques (using membrane mimics and spectroscopic methods) are used to generate insights revealing the following trends: A) The reduction of degrees of freedom in bottle brushes reduces their tendencies for self-assembly and undesired protein interaction. B) When compared to linear polymers, bottlebrushes attach to membranes faster and more efficiently as well as in a unimolecular fashion. Their multivalent presentation of linear subunits also leads to aggregation between liposomes, which is not induced by linear polymers. C) Neutron reflectometry measurements show an increased tendency of bottle brushes to insert into the hydrophobic tails of phospholipid monolayers. The knowledge about these features will fuel the future development of even more efficient antimicrobial polymers.