(485e) A Simple Kinetic Model Describing Nanoparticle Interactions With a Tethered Lipid Bilayer

In this paper, we present a simple mechanistic kinetic model to describe interactions of engineered nanomaterials (ENM) with a tethered bilayer lipid membrane (tBLM). The model was developed to help elucidate molecular processes responsible for time-dependent changes in tBLM resistance (R_m) following ENM exposure. The model uses two kinetic constants to describe the rates of ENM binding to, and lipid removal from, the tBLM. The model was fit to R_m vs. time data for interaction of a tBLM formed using 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with two types of ENM:  functionalized polypropargyl glycolide nanoparticles and functionalized polystyrene nanoparticles. The model was able to reproduce diverse trends in the R_m vs. time data, including a continuous decrease in R_m and an initial increase in R_m followed by a decrease. The model also predicted that interaction of only a few nanoparticles could generate measurable changes in the tBLM’s R_mvalue. Hierarchical clustering was applied to pairs of optimized kinetic constants for various ENM. The resulting dendrograms indicated that ENM having different properties (composition, size, surface charge) could be statistically distinguished using this approach. Results of this study provide insight into fundamental mechanisms by which ENM interact with biomembranes and may lead to improved methods to rapidly screen ENM libraries for desired functional and biosafety profiles.  

Keywords: tBLM; engineered nanomaterials; model; kinetic constant; hierarchical clustering; lipid bilayer; resistance