PMID- 33886273 OWN - NLM STAT- MEDLINE DCOM- 20210609 LR - 20230704 IS - 1936-086X (Electronic) IS - 1936-0851 (Print) IS - 1936-0851 (Linking) VI - 15 IP - 5 DP - 2021 May 25 TI - Nanoparticles Interfere with Chemotaxis: An Example of Nanoparticles as Molecular "Knockouts" at the Cellular Level. PG - 8813-8825 LID - 10.1021/acsnano.1c01262 [doi] AB - 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. FAU - Zhang, Xi AU - Zhang X AUID- ORCID: 0000-0001-5777-2368 AD - Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, Illinois 61801, United States. FAU - Falagan-Lotsch, Priscila AU - Falagan-Lotsch P AUID- ORCID: 0000-0002-0849-2682 AD - Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, Illinois 61801, United States. AD - Department of Biological Sciences, Auburn University, Auburn, Alabama 36849, United States. FAU - Murphy, Catherine J AU - Murphy CJ AUID- ORCID: 0000-0001-7066-5575 AD - Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, Illinois 61801, United States. LA - eng GR - R01 GM125845/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210422 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (Polyelectrolytes) RN - 7440-57-5 (Gold) SB - IM MH - Chemotaxis MH - Gold MH - Humans MH - *Metal Nanoparticles MH - Monocytes MH - *Nanoparticles MH - Polyelectrolytes PMC - PMC10312996 MID - NIHMS1908131 OTO - NOTNLM OT - cell migration OT - chemotaxis OT - gold nanoparticles OT - nanoparticle intervention OT - three-dimensional model COIS- The authors declare no competing financial interest. EDAT- 2021/04/23 06:00 MHDA- 2021/06/10 06:00 PMCR- 2023/06/30 CRDT- 2021/04/22 17:13 PHST- 2021/04/23 06:00 [pubmed] PHST- 2021/06/10 06:00 [medline] PHST- 2021/04/22 17:13 [entrez] PHST- 2023/06/30 00:00 [pmc-release] AID - 10.1021/acsnano.1c01262 [doi] PST - ppublish SO - ACS Nano. 2021 May 25;15(5):8813-8825. doi: 10.1021/acsnano.1c01262. Epub 2021 Apr 22.