Nanoparticle uptake and intracellular fate are often investigated from the perspective of particle properties and their effects on target cells. However, the biological context of the exposed cells can strongly influence how nanoparticles interact with them. This talk focuses on cell morphology and spatial organization as functional readouts of this context, linking morphological features at the population and intracellular levels to nanoparticle uptake and routing.

At the population level, local cell crowding, spreading, and spatial organization can affect membrane accessibility and uptake dynamics. Using bioprinted epithelial cell-density gradients, we show that differences in local density are associated with changes in nanoparticle uptake, largely explained by differences in cell spreading. These results highlight that uptake measurements depend not only on nanoparticle type and dose, but also on how cells are organized and spatially arranged.

At the intracellular level, the morphological organization of the endolysosomal system may influence how nanoparticles are taken up and processed after internalization. In polarized human macrophages, preliminary imaging suggests that distinct activation states are associated with different LAMP-1-positive lysosomal morphologies, particularly differences in lysosomal tubulation. Ongoing work investigates if and how these morphological differences are linked to nanoparticle uptake and intracellular fate.

Overall, this talk highlights how cell morphology and intracellular architecture may serve as predictive readouts of nanoparticle-cell interactions, helping to predict differences in uptake efficiency and intracellular processing.