Ergodicity breaking on the neuronal surface emerges from random switching between diffusive states

Weron, Aleksander; Burnecki, Krzysztof; Akin, Elizabeth J.; Solé, Laura; Balcerek, Michał; Tamkun, Michael M.; Krapf, Diego

doi:10.1038/s41598-017-05911-y

Cited by 86 publications

(92 citation statements)

References 43 publications

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“…If this assumption does not hold, the diffusional properties obtained by temporal averaging over a single molecule will not be equivalent to those resulting from ensemble averaging over the entire population. Many biological systems conform to this latter behavior and hence display weak ergodicity breaking (WEB), often related to transient immobilization or spatial inhomogeneities (Weigel et al ; Manzo et al ; Weron et al ). For this reason, testing the ergodic hypothesis can unravel important features of the diffusion of the protein in the membrane.…”

Section: Resultsmentioning

confidence: 99%

Antibody‐induced crosslinking and cholesterol‐sensitive, anomalous diffusion of nicotinic acetylcholine receptors

Mosqueira

Camino

Barrantes

2019

Journal of Neurochemistry

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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.

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Section: Resultsmentioning

confidence: 99%

Antibody‐induced crosslinking and cholesterol‐sensitive, anomalous diffusion of nicotinic acetylcholine receptors

Mosqueira

Camino

Barrantes

2019

Journal of Neurochemistry

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“…Even so, a consensus exists that anomalous diffusion is described as a time‐dependent diffusion coefficient, D ( t ) due to a non‐ergodic property of anomalous diffusion kinetics . Currently, a handful of methods are available to measure D ( t ) including Fluorescence Recovery after Photobleaching (FRAP), Fluorescence Correlation Spectroscopy (FCS), Single Particle Tracking (SPT) and Nuclear Magnetic Resonance (NMR) .…”

Section: Introductionmentioning

confidence: 99%

A novel computational framework for D(t) from Fluorescence Recovery after Photobleaching data reveals various anomalous diffusion types in live cell membranes

Kang

Day

Kenworthy

2019

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Diffusion of proteins and lipids in lipid membranes plays a pivotal role in almost all aspects of cellular biology, including motility, exo−/endocytosis and signal transduction. For this reason, gaining a detailed understanding of membrane structure and function has long been a major area of cell biology research. To better elucidate this structure‐function relationship, various tools have been developed for diffusion measurements, including Fluorescence Recovery After Photobleaching (FRAP). Because of the complexity of cellular microenvironments, biological diffusion is often correlated over time and described by a time‐dependent diffusion coefficient, D(t), although the underlying mechanisms are not fully understood. Since D(t) provides important information regarding cellular structures, such as the existence of subresolution barriers to diffusion, many efforts have been made to quantify D(t) by FRAP assuming a single power law, D(t) = Γt α − 1 where Γ and α are transport coefficient and anomalous exponent. However, straightforward approaches to quantify a general form of D(t) are lacking. In this study, we develop a novel mathematical and computational framework to compute the mean square displacement of diffusing molecules and diffusion coefficient D(t) from each individual time point of confocal FRAP data without the single power law assumption. Additionally, we developed an auxiliary equation for D(t) which can readily distinguish normal diffusion or single power law anomalous diffusion from other types of anomalous diffusion directly from FRAP data. Importantly, by applying this approach to FRAP data from a variety of membrane markers, we demonstrate the single power law anomalous diffusion assumption is not sufficient to describe various types of D(t) of membrane proteins. Lastly, we discuss how our new approaches can be applied to other fluorescence microscopy tools such as Fluorescence Correlation Spectroscopy (FCS) and Single Particle Tracking (SPT).

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“…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].…”

Section: Introductionmentioning

confidence: 99%

Transient subdiffusion from an Ising environment

et al. 2017

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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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Ergodicity breaking on the neuronal surface emerges from random switching between diffusive states

Cited by 86 publications

References 43 publications

Antibody‐induced crosslinking and cholesterol‐sensitive, anomalous diffusion of nicotinic acetylcholine receptors

Antibody‐induced crosslinking and cholesterol‐sensitive, anomalous diffusion of nicotinic acetylcholine receptors

A novel computational framework for D(t) from Fluorescence Recovery after Photobleaching data reveals various anomalous diffusion types in live cell membranes

Transient subdiffusion from an Ising environment

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