"If you understand something in only one way, then you don't really understand it at all."
-Marvin Minsky
The electrome is the sum of all the electrical charges (fixed, mobile, and induced) across a biological system, and the associated electrical potentials, conductances and capacitances through which they interact. It has implications from the nanoscale (ion channels and double layers) to macro scale (EEG and ECG) and impacts both on how the cell functions in isolation, how it interacts with its environment and other cells, and how ensembles of cells perform multiple biological functions.
The electrome concept arises from the fact that there are many different electrical aspects to cell biology, though biological science has largely focussed almost exclusively on those two, essential for life, that rely of electrical effects to function – the muscles and the nerves, which use depolarisation of the voltage between cell interior and exterior (the membrane potential Vm) to transmit information or to contract. Other cell types also have a voltage (called the resting membrane potential, RMP) which regulates cellular functions through the action of voltage-gated ion channels, but its function is limited to this – because the standard model of RMP considers the electric field arising from the membrane potential (which arises because of diffusion of ions across the membrane) to exist only in the membrane itself. Our work has questioned this model. By analysing multiple electrical parameters simultaneously, we have found interactions stretching for beyond the membrane itself.
Specifically, we have examined cells at different conductivities, and using three different methods – the membrane potential by flow cytometry (or the CCCP method for red blood cells); the zeta potential (the voltage a nanometre or two outside the membrane, due to the surface charge), and dielectrophoresis to yield the membrane capacitance, surface conductance and cytoplasm conductivity. These measures have been applied across several cell types, including red blood cells, platelets, chondrocytes and cancer cells. Taking these different measures and different conditions – and adding treatments to change the surface charge or membrane conductance – has yielded a new model of cell behaviour with far-reaching implications for cell function.
Our model suggests that the primary origin of the resting potential lies with the capacitive interaction between charges on the inner surface of the cell membrane, and the bulk. The ion distribution (anions and cations) at the outer surface are effected by the external surface potential, and it is these ion concentrations which then diffuses to the cytoplasm – which are then further altered by interaction with the inner membrane surface. Since dielectrophoresis (and its underpinning Clausius-Mossotti model) is interfacial, it is the conductivity at this interface that is determined by DEP. Furthermore, since these charges accumulated at the inner membrane surface are charged (being rich in cations, poor in anions) , this accumulated charge immediately at the capacitive cell membrane is what gives rise to the membrane potential. This means that the membrane potential and cytoplasm conductivity parameter are linked- and that the cytoplasm conductivity can be used to estimate the membrane potential. Furthermore, this induced potential also induces electrical charge on the outer surface of the membrane; this gives rise to an altered surface potential, which changes both the zeta potential (by up to 37% of Vm) and the surface conductance.
This has potentially huge significance in cell function. There are many instances where cell membrane potential suddenly changes in response to a stimulus that changes the way in which cells interact with their environment; for example, activating platelets and macrophages, or egg cells at the moment of fertilization, or cancer cells when they metastasize. Changing the zeta potential changes how cells interact, such as invading malarial cells; it changes the way in which cells interact with ions in their environment, so that changing Vm, and hence zeta, can confer effects similar to that observed in voltage-gated channels, simply by changing the ionic microenvironment. We also believe that these effects have significance far beyond cell-cell interaction, explaining phenomena from electrotaxis to wound healing to immune response.
Our work to develop this model continues; watch the press for developments.
" I am now about to set seriously to work upon preparing for the press an account of my theory which in its present state I look upon as the most valuable if not the only valuable contribution that I have made or am likely to make to Science and the thing by which I would desire if at all to be remembered hereafter"
-George Boole, on Boolean Algebra