Mechanisms Underlying Anomalous Diffusion in the Plasma Membrane

Krapf, Diego

doi:10.1016/bs.ctm.2015.03.002

Cited by 93 publications

(113 citation statements)

References 153 publications

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“…In theory, anomalous diffusion can be derived from generalized Langevin equations (8), fractional Brownian motion (FBM) (16),percolation (17), diffusion in fractals (18), diffusion in a heterogeneous landscape (19,20), or using power law jump size or waiting time distributions in continuous time random walk (CTRW) models (21).…”

Section: Introductionmentioning

confidence: 99%

Inferring Diffusion Dynamics from FCS in Heterogeneous Nuclear Environments

Tsekouras

Siegel

Day

et al. 2015

Biophysical Journal

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Fluorescence correlation spectroscopy (FCS) is a noninvasive technique that probes the diffusion dynamics of proteins down to single-molecule sensitivity in living cells. Critical mechanistic insight is often drawn from FCS experiments by fitting the resulting time-intensity correlation function, G(t), to known diffusion models. When simple models fail, the complex diffusion dynamics of proteins within heterogeneous cellular environments can be fit to anomalous diffusion models with adjustable anomalous exponents. Here, we take a different approach. We use the maximum entropy method to show-first using synthetic data-that a model for proteins diffusing while stochastically binding/unbinding to various affinity sites in living cells gives rise to a G(t) that could otherwise be equally well fit using anomalous diffusion models. We explain the mechanistic insight derived from our method. In particular, using real FCS data, we describe how the effects of cell crowding and binding to affinity sites manifest themselves in the behavior of G(t). Our focus is on the diffusive behavior of an engineered protein in 1) the heterochromatin region of the cell's nucleus as well as 2) in the cell's cytoplasm and 3) in solution. The protein consists of the basic region-leucine zipper (BZip) domain of the CCAAT/enhancer-binding protein (C/EBP) fused to fluorescent proteins.

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Section: Introductionmentioning

confidence: 99%

Inferring Diffusion Dynamics from FCS in Heterogeneous Nuclear Environments

Tsekouras

Siegel

Day

et al. 2015

Biophysical Journal

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“…Quantitative imaging methods, such as single-particle tracking [1–4], spatiotemporal image correlation spectroscopy [5], fluorescence correlation spectroscopy (FCS) [6,7], and stimulated emission depletion (STED)-FCS [8,9], show that the dynamics of proteins and lipids in the plasma membrane often deviate from normal diffusion. In particular, the mean square displacement (MSD) does not grow linearly in time as expected for Brownian motion [10–13]. This behavior suggests processes that hinder diffusion.…”

Section: Introductionmentioning

confidence: 99%

“…Anomalous diffusion in the plasma membrane can be caused by macromolecular crowding [14], transient binding [15], heterogeneities [16,17], and membrane compartmentalization by the underlying cytoskeleton [2,9,18,19]. In recent years, it has become evident that a single mechanism cannot account for the complex dynamics observed in the plasma membrane [13]. We have shown that interactions with clathrin coated pits (CCPs) cause anomalous diffusion and ergodicity breaking [15,20].…”

Section: Introductionmentioning

confidence: 99%

Plasma Membrane is Compartmentalized by a Self-Similar Cortical Actin Meshwork

et al. 2017

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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 to compartmentalization of the plasma membrane and that membrane proteins are transiently confined within actin fences. Furthermore, superresolution imaging shows that the cortical actin is organized into a self-similar meshwork. These results present a hierarchical nanoscale picture of the plasma membrane.

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“…However, SPT in live cells often reveals complexities accompanied by deviations from normal diffusion 10–12 . In particular the TA MSD can show a non-linear scalingwhere K α is the generalized diffusion coefficient and, for subdiffusive processes, 0 < α < 1.…”

Section: Introductionmentioning

confidence: 99%

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

Weron

Burnecki

Akin

et al. 2017

Sci Rep

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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.

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Mechanisms Underlying Anomalous Diffusion in the Plasma Membrane

Cited by 93 publications

References 153 publications

Inferring Diffusion Dynamics from FCS in Heterogeneous Nuclear Environments

Inferring Diffusion Dynamics from FCS in Heterogeneous Nuclear Environments

Plasma Membrane is Compartmentalized by a Self-Similar Cortical Actin Meshwork

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

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