Isolating the sources of heterogeneity in nano-engineered particle-cell interactions.

Nano-engineered particles have the potential to enhance therapeutic success and reduce toxicity-based treatment side effects via the targeted delivery of drugs to cells. This delivery relies on complex interactions between numerous biological, chemical and physical processes. The intertwined nature of these processes has thus far hindered attempts to understand their individual impact. Variation in experimental data, such as the number of particles inside each cell, further inhibits understanding. Here, we present a mathematical framework that is capable of examining the impact of individual processes during particle delivery. We demonstrate that variation in experimental particle uptake data can be explained by three factors: random particle motion; variation in particle-cell interactions; and variation in the maximum particle uptake per cell. Without all three factors, the experimental data cannot be explained. This work provides insight into biological mechanisms that cause heterogeneous responses to treatment, and enables precise identification of treatment-resistant cell subpopulations.