RT Journal Article SR Electronic T1 Membrane Diffusion Occurs by a Continuous-Time Random Walk Sustained by Vesicular Trafficking JF bioRxiv FD Cold Spring Harbor Laboratory SP 208967 DO 10.1101/208967 A1 Maria Goiko A1 John R. de Bruyn A1 Bryan Heit YR 2018 UL http://biorxiv.org/content/early/2018/01/10/208967.abstract AB Diffusion in cellular membranes is regulated by processes which occur over a range of spatial and temporal scales. These processes include membrane fluidity, inter-protein and inter-lipid interactions, interactions with membrane microdomains, interactions with the underlying cytoskeleton, and cellular processes which result in net membrane movement. The complex, non-Brownian diffusion that results from these processes has been difficult to characterize, and moreover, the impact of factors such as membrane recycling on membrane diffusion remains largely unexplored. We have used a careful statistical analysis of single-particle tracking data of the single-pass plasma membrane protein CD93 to show that the diffusion of this protein is well-described by a continuous-time random walk in parallel with an aging process mediated by membrane corrals. The overall result is an evolution in the diffusion of CD93: proteins initially diffuse freely on the cell surface, but over time, become increasingly trapped within diffusion-limiting membrane corrals. Stable populations of freely diffusing and corralled CD93 are maintained by an endocytic/exocytic process in which corralled CD93 is selectively endocytosed, while freely diffusing CD93 is replenished by exocytosis of newly synthesized and recycled CD93. These results provide insight into the nature of the biological and biophysical processes that can lead to significantly non-Brownian diffusion of membrane proteins, and demonstrate that ongoing membrane recycling is critical to maintaining steady-state diffusion in the plasma membrane.AbbreviationsCHOChinese Hamster Ovary cells.CTRWContinuous Time Random Walk.EA-MSDEnsemble-Averaged Mean Squared Displacement.EA-TAMSDEnsemble-Averaged Time-Averaged Mean Squared Displacement.FBMFractional Brownian Motion.MMEMean Maximal Excursion.MSDMean Squared Displacement.MSSMoment Scaling Spectrum.SPTSingle Particle Tracking.TAMSDTime-Averaged Mean Squared Displacement.