(663c) Cellular Heteorgeneity in Endocytic Nanoarticle Uptake: Dissecting the Origin Using Quantitative Experiments and Modeling

Mammalian cells employ various endocytic components (transporters) in the cell plasma membrane to mediate the intake of extracellular molecules and particles. The level of expression of these transporters in individual cells determines the cell-to-cell variability in uptake rates. However, in addition to the transporter expression, the size of a cell may also be an important parameter governing the uptake rate. A larger cell presents a larger surface area and may express more transporters in the plasma membrane. Therefore, the cell-to-cell variability in the uptake of an external material may reflect the combined contributions of cell size, level of transporter expression and an undefined dependency between these two. Here, using quantitative single-cell experiments and modeling, we investigate these two parameters in determining the overall heterogeneity in nanoparticle uptake by MDA-MB 231 breast cancer cells. We also characterize their interdependencies. Based on the analysis of our experimental data and parameter values, we formulate a kinetic model of particle uptake by single cells. The model captures cell size and the level of transporter expression in the cell plasma membrane. The model accurately predicts the kinetic and steady-state particle uptake behaviors of MDA-MB 231 cancer cells in a cell culture medium.