Real-Time Nanoparticle–Cell Interactions in Physiological Media by Atomic Force Microscopy

Abstract

Particle–cell interactions in physiological media are important in determining the fate and transport of nanoparticles and biological responses to them. In this work, these interactions are assessed in real time using a novel atomic force microscopy (AFM) based platform. Industry-relevant CeO2 and Fe2O3 engineered nanoparticles (ENPs) of two primary particle sizes were synthesized by the flame spray pyrolysis (FSP) based Harvard Versatile Engineering Nanomaterials Generation System (Harvard VENGES) and used in this study. The ENPs were attached on AFM tips, and the atomic force between the tip and lung epithelia cells (A549), adhered on a substrate, was measured in biological media, with and without the presence of serum proteins. Two metrics were used to assess the nanoparticle cell: the detachment force required to separate the ENP from the cell and the number of bonds formed between the cell and the ENPs. The results indicate that these atomic level ENP–cell interaction forces strongly depend on the physiological media. The presence of serum proteins reduced both the detachment force and the number of bonds by approximately 50% indicating the important role of the protein corona on the particle cell interactions. Additionally, it was shown that particle to cell interactions were size and material dependent.

A Critical Review of in Vitro Dosimetry for Engineered Nanomaterials

“…ENMs suspended in complex physiological media may flocculate, agglomerate, dissolve and interact with serum components [27,[39][40][41] in a manner largely dependent on the dispersion preparation protocol, particle characteristics such as primary particle size, shape, chemical composition and surface chemistry [42][43][44][45], as well as media properties such as ionic strength, pH and protein content [42,43,46]. In order to optimize ENM dispersibility in suspension, ultrasonic energy is used in a process known as sonication, wherein sound waves are propagated in liquid media, leading to alternating high-pressure (compression) and low-pressure (rarefaction) cycles [26].…”

“…The effective density of nanomaterial agglomerates can differ from the density of the raw material by as much as several fold, primarily because of the irregular and fractal quality of nanomaterial primary particles that leads to intraparticle trapping of culture media [56] and the corona of adsorbed protein that coats the surface of the primary particles [44,45,57]. Because effective density is directly proportional to the rate of agglomerate sedimentation, its accurate measurement is key to estimating delivered dose over time in vitro.…”

The role of the food matrix and gastrointestinal tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps

“…the protein corona)(DeLoid et al , 2014). The effect of the protein coronoa on nano-bio interactions is well understood and noted in the nanotoxicology research(Kelly et al , 2015; Monopoli et al , 2011a; Pyrgiotakis et al , 2014; Pyrgiotakis et al , 2013). …”

“…The properties of pristine nanoparticles in a simple powder or liquid can usually be characterized using existing methodologies: light, electron or atomic force microscopy for microstructure and aggregation state (Pyrgiotakis et al , 2014; Pyrgiotakis et al , 2013); dynamic or static light scattering for particle size distribution; tunable resistive pulse sensing technology for particle size and charge (Pal et al , 2014); microelectrophoresis for particle charge; and, chromatography, mass spectrometry, or NMR for particle composition.…”

“…, chemical reactivity, mechanical strength, digestibility, transport properties, and cellular uptake, accumulation, and distribution (Acosta, 2009; Buzea et al , 2007; Cohen et al , 2014a; Davidson et al , 2016; Konduru et al , 2015; Konduru et al , 2014; Konduru et al , 2016; Lu et al , 2016a; Lu et al , 2016b; Ma et al , 2015; Pirela et al , 2016a; Pirela et al , 2016b; Sisler et al , 2015; Sotiriou et al , 2014; Watson et al , 2014; Yokel et al , 2014; Zhou et al , 2014). These changes are associated with the smaller particle dimensions and higher surface areas of nanoparticles compared to larger particles, as well as to quantum effects taking place in the nanoscale (Pyrgiotakis et al , 2014; Pyrgiotakis et al , 2013). …”