Nanoparticles Interfere with Chemotaxis: An Example of Nanoparticles as Molecular "knockouts" at the Cellular Level

Engineered colloidal nanoparticles show great promise in biomedical applications. While much of the work of assessing nanoparticle impact on living systems has been focused on the direct interactions of nanoparticles with cells/organisms, indirect effects via the extracellular matrix have been observed and may provide deeper insight into nanoparticle fate and effects in living systems. In particular, the large surface area of colloidal nanoparticles may sequester molecules from the biological milieu, make these molecules less bioavailable, and therefore function indirectly as "molecular knockouts"to exert effects at the cellular level and beyond. In this paper, the hypothesis that molecules that control cellular behavior (in this case, chemoattract molecules that promote migration of a human monocytic cell line, THP-1) will be less bioavailable in the presence of appropriately functionalized nanoparticles, and therefore the cellular behavior will be altered, was investigated. Three-dimensional chemotaxis assays for the characterization and comparison of THP-1 cell migration upon exposure to a gradient of monocyte chemoattractant protein-1 (MCP-1), with and without gold nanoparticles with four different surface chemistries, were performed. By time-lapse microscopy, characteristic parameters for chemotaxis, along with velocity and directionality of the cells, were quantified. Anionic poly(sodium 4-styrenesulfonate)-coated gold nanoparticles were found to significantly reduce THP-1 chemotaxis. Enzyme-linked immunosorbent assay results show adsorption of MCP-1 on the poly(sodium 4-styrenesulfonate)-coated gold nanoparticle surface, supporting the hypothesis that adsorption of chemoattractants to nanoparticle surfaces interferes with chemotaxis. Free anionic sulfonated polyelectrolytes also interfered with cell migrational behavior, showing that nanoparticles can also act as carriers of chemotactic-interfering molecules.