Field model for multistate lateral diffusion of various transmembrane proteins observed in living Dictyostelium cells

The lateral diffusion of transmembrane proteins on plasma membranes is a fundamental process for various cellular functions. Diffusion properties specific for individual protein species have been extensively studied, but the common features among protein species are poorly understood. Here, we systematically studied the lateral diffusion of various transmembrane proteins in the lower eukaryote Dictyostelium discoideum cells using a hidden Markov model for single-molecule trajectories obtained experimentally. As common features, all membrane proteins that had from one to ten transmembrane regions adopted three free diffusion states with similar diffusion coefficients regardless of their structural variability. All protein species reduced their mobility similarly upon the inhibition of microtubule or actin cytoskeleton dynamics, or myosin II. The relationship between protein size and the diffusion coefficient was consistent with the Saffman–Delbrück model, meaning that membrane viscosity is a major determinant of lateral diffusion, but protein size is not. These protein species-independent properties of multistate free diffusion were explained simply and quantitatively by free diffusion on the three membrane regions with different viscosities, which is in sharp contrast to the complex diffusion behavior of transmembrane proteins in higher eukaryotes.