Nanoparticle-Decorated Erythrocytes Reveal That Particle Size Controls the Extent of Adsorption, Cell Shape, and Cell Deformability

Unraveling the interaction of nanoparticles with living cells is fundamental for nanomedicine and nanotoxicology. Erythrocytes are abundant and serve as model cells with well-characterized properties. Quantitative experiments addressing the binding of carboxylated polystyrene nanoparticles to human erythrocytes reveal saturated adsorption with only sparse (∼2%) coverage of the cell membrane by partial-wrapped nanoparticles. The independence of the adsorbed area on particle size suggests a restricted number of adhesive sites on the membrane. Using a continuum membrane model combined with nanoparticle–membrane adhesion mediated by receptor–ligand bonds, we predict high bond energies and low receptor densities for partial-wrapped particles. With the help of computer simulations, we determine sets of receptor densities, receptor diffusion coefficients, minimal numbers of bound receptors required for multivalent binding, and maximal possible numbers of bound receptors that reproduce the experimental nanoparticle adsorption data. Nanoparticle decoration of erythrocytes leads to shape transformations and reduced cell deformability. We quantitatively characterize and interpret erythrocyte shape and deformability changes. The shape changes also offer insights into the modification of the mechanical properties of other mammalian cell membranes by adhered nanoparticles. A potential application of nanoparticle-loaded erythrocytes is retarded targeted drug delivery with a long lifetime of the particles in the blood circulation.