Dynamics of membrane potential oscillations in biological cells
Early Stage Researcher: Aleksandra Pidde
Principle Investigators: Aneta Stefanovska (Lancaster, ULANC – major institution), Ernest Montbrio and Ralph G Andrzejak (Barcelona, UPF – partner institution)
Every living cell continuously maintains its membrane potential by carefully adjusting the concentrations of potassium, sodium, chloride and other anions inside the cell. Based on Boltzmann statistics and taking account of drift and diffusion forces, the Nernst-Plank and Goldman equations were proposed to describe the membrane potential. They are valid for stationary or equilibrium states. But a living cell, whether excitable or non-excitable, is in a state of continuous exchange of ions across the membrane, even when unperturbed. Therefore, the physics of the membrane potential needs to be revised – in the light of novel experimental data based on functional monitoring of membrane potential using patch clamp method or fluorescence-based methods for measurement of molecular dynamics in living cells.
This project aims to propose a new physics of the living cell. It will achieve this ambitious aim by combining the physics of non-autonomous dynamical systems with numerical analysis and experimental data. It will analyse the dynamical changes that occur in the cell membrane potential as ions cross the membrane, in order to construct the laws that govern cellular function and to infer how they go wrong in diseases like cancer. The project will involve the newly developed theory of chronotaxic (from Greek chronos – time and taxis – order) systems. These systems, proposed by Lancaster, are able to stabilise the rates at which they exchange energy and matter with the environment and thus preserve stable oscillation frequencies in the biophysical processes that sustain life. The corresponding oscillations can be measured and analysed. State-of-the-art time-frequency methods, nonlinear decomposition methods, and ridge extraction methods will be applied in the analysis. We hypothesise that when this stability is lost or changed the cell becomes dysfunctional, resulting in cell death or in diseases like cancer. The new theory will also be used in modelling networks of neuronal systems.
- D Junge D: Nerve and Muscle Excitation (2nd edition ed.). Sunderland, Massachusetts: Sinauer Associates. pp. 33–37, 1981. ISBN0-87893-410-3.
- DE Goldman: Potential, impedance and rectification in membranes, J Gen Physiol 27:37-60, 1943. doi:10.1085/jgp.27.1.37
- YF Suprunenko, A Stefanovska: Generalized chronotaxic systems: Time-dependent oscillatory dynamics stable under continuous perturbation, Phys Rev E 90: 032921, 2014
- PT Clemson, YF Suprunenko, T Stankovski, A Stefanovska: Inverse approach to chronotaxic systems for single-variable time series, Phys Rev E 89: 032904, 2014
- YF Suprunenko, PT Clemson, A Stefanovska: Chronotaxic systems: A new class of self-sustained nonautonomous oscillators, Phys Rev Lett 111: 024101, 2013
- PT Clemson, A Stefanovska: Discerning non-autonomous dynamics, Phys Rep 542: 297-368, 2014
- DG Spiller, CD Wood, DA Rand, MRH White, Measurement of single-cell dynamics, Nature 465: 736-745, 2010. DOI: 10.1038/nature09232