While positively charged nanomaterials
induce cytotoxicity in many
organisms, much less is known about how the spatial distribution and
presentation of molecular surface charge impact nanoparticle–biological
interactions. We systematically functionalized diamond nanoparticle
surfaces with five different cationic surface molecules having different
molecular structures and conformations, including four small ligands
and one polymer, and we then probed the molecular-level interaction
between these nanoparticles and bacterial cells. Shewanella
oneidensis MR-1 was used as a model bacterial cell system
to investigate how the molecular length and conformation of cationic
surface charges influence their interactions with the Gram-negative
bacterial membranes. Nuclear magnetic resonance (NMR) and X-ray photoelectron
spectroscopy (XPS) demonstrate the covalent modification of the nanoparticle
surface with the desired cationic organic monolayers. Surprisingly,
bacterial growth-based viability (GBV) and membrane damage assays
both show only minimal biological impact by the NPs functionalized
with short cationic ligands within the concentration range tested,
yet NPs covalently linked to a cationic polymer induce strong cytotoxicity,
including reduced cellular viability and significant membrane damage
at the same concentration of cationic groups. Transmission electron
microscopy (TEM) images of these NP-exposed bacterial cells show that
NPs functionalized with cationic polymers induce significant membrane
distortion and the production of outer membrane vesicle-like features,
while NPs bearing short cationic ligands only exhibit weak membrane
association. Our results demonstrate that the spatial distribution
of molecular charge plays a key role in controlling the interaction
of cationic nanoparticles with bacterial cell membranes and the subsequent
biological impact. Nanoparticles functionalized with ligands having
different lengths and conformations can have large differences in
interactions even while having nearly identical zeta potentials. While
the zeta potential is a convenient and commonly used measure of nanoparticle
charge, it does not capture essential differences in molecular-level
nanoparticle properties that control their biological impact.
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