Exploring the Interactions Between Methyl Methacrylate Polymers and the Bacterial Outer Membrane via Coarse-Grained Molecular Dynamics Simulations

Polymer brush coatings offer a promising strategy for combating bacterial adhesion and biofilm formation in medical devices. However, a detailed molecular understanding of how different brush chemistries interact with bacterial membranes remains incomplete. In this study, we use coarse-grained steered molecular dynamics and umbrella sampling simulations to investigate the interaction and translocation process of four methyl methacrylate-derived polymers: pDMAEMA (weak cationic), pMETAC (strong cationic), pMEDSAH (zwitterionic), and pSPMA (anionic), through a bacterial outer membrane (OM) model ofEscherichia coli. The simulations reveal a four-step translocation process: approach, adhesion, permeation, and internalization, characterized by distinct thermodynamic and kinetic signatures. Cationic polymers exhibit a pronounced favorable adhesion with the OM surface, especially with the saccharide inner core domain of the LPS molecules, which is mainly attributed to their favorable electrostatic interactions. The dragging of LPS units to the inner leaflet of the bacterial OM was also distinguished in the translocation of these positively charged polymers. In contrast, zwitterionic and anionic polymers show less favorable adhesion, consistent with their antifouling behavior. This approach provides a computational framework to resolve the free-energy landscapes and structural perturbations associated with polymer-membrane interactions at molecular detail, including the prediction of kinetically unfavorable processes, such as the permeation and internalization of the polymer in the intracellular region of the membrane. These results offer mechanistic insights into how hydration, charge, and polymer structure influence bacterial membrane interactions, advancing the molecular design of antifouling and antibacterial surface coatings.