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

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

doi:10.1038/s41598-017-05911-y

Abstract

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.

Highlights

The stochastic motion of molecules in living cells is essential to maintain a myriad of physiological processes
Note that NavPaS lacks more than 400 cytoplasmic amino acids as compared to the Nav1.6 channel studied in the present work
Weak ergodicity breaking has been priorly found in cell membranes due to transient binding[16] and heterogeneous diffusion landscapes[17]

Summary

Introduction

The stochastic motion of molecules in living cells is essential to maintain a myriad of physiological processes. While diffusion naturally mixes cell components, the cellular environment must be organized in order to maintain a living state. This process is typically fulfilled by actively bringing the system out of thermodynamic equilibrium. In the plasma membrane of human embryonic kidney (HEK) cells, ion channels exhibit non-ergodic behaviour because they bind to clathrin-coated pits with a heavy-tailed distribution of immobilization times[7, 16]. The DC-SIGN receptor motion shows ergodicity breaking on the surface of CHO cells caused by heterogeneous dynamics with frequent changes of diffusivity[17]. Ergodicity breaking caused by bulk-mediated diffusion was observed in reconstituted lipid bilayers[18]

Methods

Results

Conclusion