Copy of Prof Sally Brooker Seminar

"Cationic Antimicrobial Polymers: Architecture & Amphiphilicity "

C5.21, Chemistry, 11:00, Tuesday 15 July 2025

Abstract

Steadily increasing levels of antimicrobial resistance (AMR) are a continuous threat to our global public health. Antimicrobial polymers (APs) offer a promising solution, as their mechanism of action – the permeabilization of bacterial membranes – is unsusceptible toward AMR. However, their selectivity between eukaryotic and prokaryotic cells is still insufficient for clinical applications.

To guide APs and direct their activity against prokaryotic cells, a plethora of parameters can be altered. The amphiphilic balance, molecular weight, or the type of charged unit are among them. One additional important aspect in this context is the polymer architecture, as it fundamentally changes the physico-chemical properties of APs. Using bottle brush copolymers as a platform for APs, we could show that confinement and multivalence in such structures has a profound impact on their biological activity.^[1-2] Indeed, optimizing structural parameters yields highly selective APs featuring increased antimicrobial activity and markedly different membrane interaction^.[3-4] Systematic variation of the aspect ratio of such molecular brushes led to a further increase in bioactivity and revealed the strong influence of intramolecular self-assembly on membrane interaction.^[5]

The use of advanced synthetic methods leading to complex macromolecules paired with the utilization of various analytical techniques generating more insight in polymer membrane interaction we aim to open new ways to APs with increased activity and lowered unspecific toxicity paving the way to APs in biomedical applications.

References:

1. Laroque, S.; Reifarth, M.; Sperling, M.; Kersting, S.; Klöpzig, S.; Budach, P.; Storsberg, J.; Hartlieb, M.; Impact of Multivalence and Self-Assembly in the Design of Polymeric Antimicrobial Peptide Mimics. ACS Appl. Mater. Interfaces 2020, 12, 30052. doi.org/10.1021/acsapm.1c00024
2. Lehnen, A.-C.; Bapolisi, A. M.; Krass, M.; AlSawaf, A.; Kurki, J.; Kersting, S.; Fuchs, H.; Hartlieb, M.; Shape matters: Highly selective Antimicrobial Bottle Brush copolymers via a one-pot RAFT polymerization approach. Biomacromolecules 2022, 23, 5350. doi.org/10.1039/D2SC05197D
3. Bapolisi, A. M.; Kielb, P.; Bekir, M.; Lehnen, A.-C.; Radon, C.; Laroque, S.; Wendler, P.; Müller-Werkmeister, H. M.; Hartlieb, M.; Antimicrobial Polymers of Linear and Bottlebrush Architecture: Probing the Membrane Interaction and Physicochemical Properties. Macromol. Rapid Commun. 2022, 43, 2200288. doi.org/10.1002/marc.202200288
4. Bapolisi, A. M.; Lehnen, A.-C.; Machatschek, R.; Mangiapia, G.; Mark, E.; Moulin, J.-F.; Wendler, P. S.; Hall, C. L.; Hartlieb, M.; Antimicrobial Polymers at the Membrane Interface: Impact of Macromolecular Architecture. Small, 2024, 10.1002/smll.202406534
5. Lehnen, A.-C.; Kogikoski Jr., S.; Stensitzki, T.; AlSawaf, A.; Bapolisi, A. M.; Wolff, M.; De Breuck, J.; Müller-Werkmeister, H.; Chiantia, S.; Bald, I.; Leiske, M. N.; Hartlieb, M.; Anisotropy in Antimicrobial Bottle Brush Copolymers and its Influence on Biological Activity. Adv. Funct. Mater., 2024, 34, 2312651, doi.org/10.1002/adfm.202312651

Polymeric Biomaterials - University of Potsdam