Abstract:A broad range of membrane proteins display anomalous diffusion on the cell surface. Different methods provide evidence for obstructed subdiffusion and diffusion on a fractal space, but the underlying structure inducing anomalous diffusion has never been visualized because of experimental challenges. We addressed this problem by imaging the cortical actin at high resolution while simultaneously tracking individual membrane proteins in live mammalian cells. Our data confirm that actin introduces barriers leading… Show more
“…We observe that the distribution of α for the whole trajectories is a mixture of two separated states: free and confined. The TA MSD subdiffusive behaviour of the free parts is characteristic of antipersistent random walks, such as diffusion on a fractal environment 32, 33 or fractional Brownian motion 34, 35 .Figure 5Histograms of TA MSD exponents per trajectory for ( a ) Nav1.6, ( b ) Kv1.4, and ( c ) CD4. The anomalous exponents α are computed for whole trajectories.…”
Stochastic motion on the surface of living cells is critical to promote molecular encounters that are necessary for multiple cellular processes. Often the complexity of the cell membranes leads to anomalous diffusion, which under certain conditions it is accompanied by non-ergodic dynamics. Here, we unravel two manifestations of ergodicity breaking in the dynamics of membrane proteins in the somatic surface of hippocampal neurons. Three different tagged molecules are studied on the surface of the soma: the voltage-gated potassium and sodium channels Kv1.4 and Nav1.6 and the glycoprotein CD4. In these three molecules ergodicity breaking is unveiled by the confidence interval of the mean square displacement and by the dynamical functional estimator. Ergodicity breaking is found to take place due to transient confinement effects since the molecules alternate between free diffusion and confined motion.
“…We observe that the distribution of α for the whole trajectories is a mixture of two separated states: free and confined. The TA MSD subdiffusive behaviour of the free parts is characteristic of antipersistent random walks, such as diffusion on a fractal environment 32, 33 or fractional Brownian motion 34, 35 .Figure 5Histograms of TA MSD exponents per trajectory for ( a ) Nav1.6, ( b ) Kv1.4, and ( c ) CD4. The anomalous exponents α are computed for whole trajectories.…”
Stochastic motion on the surface of living cells is critical to promote molecular encounters that are necessary for multiple cellular processes. Often the complexity of the cell membranes leads to anomalous diffusion, which under certain conditions it is accompanied by non-ergodic dynamics. Here, we unravel two manifestations of ergodicity breaking in the dynamics of membrane proteins in the somatic surface of hippocampal neurons. Three different tagged molecules are studied on the surface of the soma: the voltage-gated potassium and sodium channels Kv1.4 and Nav1.6 and the glycoprotein CD4. In these three molecules ergodicity breaking is unveiled by the confidence interval of the mean square displacement and by the dynamical functional estimator. Ergodicity breaking is found to take place due to transient confinement effects since the molecules alternate between free diffusion and confined motion.
“…The turning angle distribution as a function of the time lags has been employed to search for correlations in the particles´ displacements (Burov et al ) (Sadegh et al ). We applied this analysis to follow the directional changes in individual nAChR trajectories using the relative angles distended by the molecules along their walk in successive time intervals, a parameter which can help distinguish among different types of anomalous subdiffusive mechanisms, for example, the so‐called fractional Brownian motion (fBM) and obstructed diffusion (OD) models.…”
Synaptic strength depends on the number of cell‐surface neurotransmitter receptors in dynamic equilibrium with intracellular pools. Dysregulation of this homeostatic balance occurs, for example in myasthenia gravis, an autoimmune disease characterized by a decrease in the number of postsynaptic nicotinic acetylcholine receptors (nAChRs). Monoclonal antibody mAb35 mimics this effect. Here we use STORM nanoscopy to characterize the individual and ensemble dynamics of monoclonal antibody‐crosslinked receptors in the clonal cell line CHO‐K1/A5, which robustly expresses adult muscle‐type nAChRs. Antibody labeling of live cells results in 80% receptor immobilization. The remaining mobile fraction exhibits a heterogeneous combination of Brownian and anomalous diffusion. Single‐molecule trajectories exhibit a two‐state switching behavior between free Brownian walks and anticorrelated walks within confinement areas. The latter act as permeable fences (~34 nm radius, ~400 ms lifetime). Dynamic clustering, trapping, and immobilization also occur in larger nanocluster zones (120–180 nm radius) with longer lifetimes (11 ± 1 s), in a strongly cholesterol‐sensitive manner. Cholesterol depletion increases the size of the clustering phenomenon; cholesterol enrichment has the opposite effect. The disclosed high proportion of monoclonal antibody‐crosslinked immobile receptors, together with their anomalous, cholesterol‐sensitive diffusion and clustering, provides new insights into the antibody‐enhanced antigenic modulation that leads to physiopathological internalization and degradation of receptors in myasthenia.
“…These consist in introducing a particle in a two dimensional Ising lattice, which -through a random walk -explores the distribution of domains (5), thus performing the motion whose mean square displacement is predicted by Eq. (9). However, as with many other complex systems, an exact simulation of the previous behavior has a high computational cost and introduces a finite-size effect to the Ising lattice.…”
Section: Infinite Ising Environment At Criticalitymentioning
confidence: 99%
“…Examples are transient binding [6], heterogeneities [7,8], membrane compartmentalization by the actin cytoskeleton [9] and macromolecular crowding [10]. Besides membrane proteins, the lipids -the most abundant components of the * miguel.garcia-march@icfo.es cell membrane -contribute to this heterogeneous organization by interacting with cholesterol, proteins and the cytoskeleton in order to partition the membrane [11], as a consequence of these dynamic interactions, also lipids exhibit non-Brownian diffusion behavior [12].…”
We introduce a model, in which a particle performs a continuous time random walk (CTRW) coupled to an environment with Ising dynamics. The particle shows locally varying diffusivity determined by the geometrical properties of the underlying Ising environment, that is, the diffusivity depends on the size of the connected area of spins pointing in the same direction. The model shows anomalous diffusion when the Ising environment is at critical temperature. We show that any finite scale introduced by a temperature different from the critical one, or a finite size of the environment, cause subdiffusion only during a transient time. The characteristic time, at which the system returns to normal diffusion after the subdiffusive plateau depends on the limiting scale and on how close the temperature is to criticality. The system also displays apparent ergodicity breaking at intermediate time, while ergodicity breaking at longer time occurs only under the idealized infinite environment at the critical temperature.
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