Surface physical cues mediate the uptake of foreign particles by cancer cells

This study examines how substrate stiffness modulates the ability of cancer cells to internalize foreign microparticles through mechanically mediated uptake mechanisms. Using polyacrylamide and silicone substrates spanning physiologically relevant stiffnesses, the authors demonstrate a non-monotonic (“meandering”) dependence of particle uptake on surface rigidity in pancreatic and breast cancer cell lines. Mechanical characterization of the substrates confirmed well-defined elastic moduli, enabling systematic correlation between surface mechanics, cell spreading, metabolic activity, and uptake efficiency. Molecular analysis revealed an inverse relationship between phosphorylated paxillin expression and particle uptake, identifying passive particle adhesion as the rate-limiting step in phagocytic-like internalization. These findings establish substrate mechanics as a critical regulator of cancer cell uptake behavior with implications for drug delivery and mechanobiology.