Morphology-dependent interaction of silica nanoparticles with intestinal cells: Connecting shape to barrier function

The intestinal compartment ensures nutrient absorptionand barrierfunction against pathogens. Despite decades of research on the complexityof the gut, the adaptive potential to physical cues, such as thosederived from interaction with particles of different shapes, remainsless understood. Taking advantage of the technological versatilityof silica nanoparticles, spherical, rod-shaped, and virus-like materialswere synthesized. Morphology-dependent interactions were studied ondifferentiated Caco-2/HT29-MTX-E12 cells. Contributions of shape,aspect ratio, surface roughness, and size were evaluated consideringthe influence of the mucus layer and intracellular uptake pathways.Small particle size and surface roughness favored the highest penetrationthrough the mucus but limited interaction with the cell monolayerand efficient internalization. Particles of a larger aspect ratio(rod-shaped) seemed to privilege paracellular permeation and increasedcell-cell distances, albeit without hampering barrier integrity.Inhibition of clathrin-mediated endocytosis and chemical modulationof cell junctions effectively tuned these responses, confirming morphology-specificinteractions elicited by bioinspired silica nanomaterials.