Single Particle Tracking of Complex Diffusion in Membranes: Simulation and Detection of Barrier, Raft, and Interaction Phenomena

Single particle tracking is being used increasingly to follow the motion of membrane-associated receptors
and lipids. Anomalous and complex diffusive behaviors are generally found in cell membranes. We developed
computational algorithms to simulate particle trajectories and to detect complex diffusive behaviors in two
dimensions, including confined and convective diffusion, intramembrane barrier and raft phenomena, and
interparticle interactions. Little useful information regarding barrier, raft, and interaction effects were provided
by standard computational procedures for identification of anomalous diffusion, including analysis of mean
squared displacement, distributions of diffusion rates and range, and time evolution of particle position. New
algorithms were developed and optimized to detect complex diffusive behaviors from simulated single particle
trajectories. A barrier detection algorithm was developed on the basis of spatial averaging of particle positions
in trajectories. A raft detection algorithm utilized spatially resolved diffusion coefficients and particle density
functions. An interaction algorithm utilized interparticle distance distributions. The algorithms developed
here are applicable to identify biologically important diffusive phenomena in cell membranes.