Reversible coating of cells with synthetic polymers for mechanochemical regulation of cell adhesion

The chemical control of cell-cell interactions using synthetic materials is useful for a wide range of biomedical applications. Herein, we report a method to regulate cell adhesion and dispersion by introducing repulsive forces to live cell membranes. To induce repulsion, we tethered amphiphilic polymers, such as cholesterol-modified polyethylene glycol (PEG-CLS) to cell membranes. These amphiphilic polymers both bind to and dissociate rapidly from membranes and thus, enable the reversible coating of cells by mixing and washout without requiring genetic manipulation or chemical synthesis in the cells. We found that the repulsive forces introduced by these tethered polymers can induce cell detachment from a substrate and allow cell dispersion in a suspension, modulate the speed of cell migration, and improve the separation of cells from tissues. Our analyses showed that coating the cells with tethered polymers most likely generated two distinct repulsive forces, lateral tension and steric repulsion, on the surface, which can be tuned by altering the polymer size and density. We also modeled how these two forces can be generated in kinetically distinctive manners to explain the various responses of cells to the coating. Collectively, our observations and analyses show how we can mechanochemically regulate cell adhesion and dispersion and may contribute to the optimization of chemical coating strategies for regulating various types of cell-cell interacting systems.