Modelling the Effects of Particle Surface Loading on Uptake and Cell Deformation

Interactions of nano- and micron-sized particles with cell membranes underpins many modern biomedical processes, particularly in drug delivery and cell therapies. When a particle adheres to the cell surface through specific or non-specific interactions, one seeks to determine the degree of wrapping as a function of various biophysical parameters. However, it is usually unclear how the cell deformation is altered by particle adhesion, which may affect, for example, membrane stability, particle uptake, cell agglutination, or even the flow of erythrocytes in blood vessels. Furthermore, current models generally consider only individual particle-membrane interactions, a situation which is rarely relevant in biomedicine for engineered cells. To study these questions, we have developed a semi-analytical model of multiple particles attaching to a cell membrane at a particular surface fraction. This model incorporates both bending and dilatation of the membrane and can predict changes in the degree of wrapping and energy landscape for a wide range of particle sizes and adhesion strengths. Beyond mechanistic insights into particle loading on cell surfaces, we also demonstrate that our model can predict the shear-rate and size-dependent detachment of nanoparticles from erythrocytes in flow and can reproduce experimental particle adsorption isotherms and endocytosis rates. We hope to apply our model to optimize cell therapy design parameters and particle loading in drug delivery to advance biomedicine.