“Waltz” of Cell Membrane-Coated Nanoparticles on Lipid Bilayers: Tracking Single Particle Rotation in Ligand–Receptor Binding

Understanding the binding of nanoparticles to receptors on biomembranes is critical to the development and screening of therapeutic materials. A prevailing understanding is that multivalent ligand-receptor binding leads to slower and confined translational motion of nanoparticles. In contrast, we report in this study distinct types of rotational dynamics of nanoparticles during their seemingly similar translational confinements in ligand-receptor binding. Our nanoparticles are fluorescently anisotropic and camouflaged with T cell membranes. As they bind to ligands on planar lipid bilayers, the particles transition from back-and-forth rocking motion to circling and eventually confined circling motion, while "hopping" between translational confinements. Both rotational and translational motions of the nanoparticles become more confined at higher ligand density. The time-dependent changes in particle rotation reveal different stages in the progression of multivalent binding between the cell-membrane coated nanoparticles and their ligands. Our work also demonstrates the promise of using combined rotational and translational single particle tracking to resolve biological interactions that could be "hidden" in translational measurements alone.