DECIPHERING THE MOLECULAR MECHANISMS OF BACTERIAL OUTER MEMBRANE VESICLES ADSORPTION AND DESORPTION ON POLYMER BRUSHES THROUGH STEERED MOLECULAR DYNAMICS

The coating of implantable medical devices with methyl-methacrylate-based polymer
brushes has emerged as a promising strategy to prevent or reduce bacterial
adhesion and subsequent biofilm formation, thereby minimizing implant-assoctiated
infections. Among these materials, poly(N,N-dimethyllaminoethylmethacrylate)
(pDMAEMA) is a pH-responsive brush that exhibits a cationic character under
physiological conditions (pH=~7.4) and possesses antibacterial activity. In contrast,
poly([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium) (pMEDSAH) is a
zwitterionic brush with outstanding antifouling properties. Despite the promising
performance of these polymer coatings in experimental studies, the molecular
mechanisms governing bacteria-polymer brush interface remain poorly understood.
In this context, this study employs steered molecular dynamics (SMD) simulations as
a computational analogue of atomic force microscopy (AFM) spectroscopy to
investigate the adsorption and desorption of bacterial outer membrane vesicles
(OMV) on pDMAEMA and pMEDSAH brushes. Here, OMV serve as molecular
models of the Gram-negative bacteria outer membrane (OM), enabling the
characterization of the molecular interactions and properties governing these OM-
brush interfaces. SMD simulations were used to calculate the pulling force profiles
associated with OMV adsorption to and desorption from the polymer brushes. The
resulting force profiles revealed rapid adorption and strong resistance to desorption
on pDMAEMA, whereas OMVs exhibited slower adsortion and lower desorption
forces on pMEDSAH. Simulations indicated that OMVs penetrate more deeply into
the pDMAEMA brush than into the pMEDSAH brush, resulting in a greater
compression of the pDMAEMA layer, as evidenced by a larger reduction in brush
thckness. The OMV underwent more pronounced structural changes upon
interaction with pDMAEMA brush than with pMEDSAH brush, as evidenced by
greater vesicle deformation in the 2D curvature order parameter maps, and a larger
reduction in OMV thickness. This mechanical effect may be associated to the
antibacterial activity of pDMAEMA. In contrast, the OMV remained structurally more
stable upon interaction with pMEDSAH, consistent with its antifouling property.