(188dg) A modeling and experimental investigation of the correlation between cell size nanoparticle uptake at the single-cell level

There is a growing interest in understanding the mechanisms whereby a cell mediates uptake of nanoparticles. Recent studies have focused on studying how various physicochemical attributes of a nanoparticle, such as particle size, shape, or surface chemistry, determine its cellular uptake. In contrast, however, little work has been done to understand how a cell’s physical attributes might govern its ability of particle uptake. This works adopted an integrative modeling and experimental approach to quantitatively elucidate the correlation between the size of individual cells and their ability to uptake nanoparticles. We developed a simple model to analyze this relationship. Using flow cytometry and fluorescence microscopy, we characterized the size distribution of MDA-MB-231 breast cancer cells and measured the uptake of nanoparticles. We then used our model to identify key parameters that correlate the size of individual cells to its ability of particle uptake in both diffusion and reaction-controlled regimes. Our analysis suggests that, in a typical experimental or physiological condition, particle uptake occurs more or less in the reaction-controlled regime. However, the effect of diffusion may also become apparent in large cells. We show that, in the reaction-limited case, there could be large cell-to-cell variation in the particle uptake rate. In contrast, this noise is diminished in the diffusion-limited regime.