Coulomb Interactions between Cytoplasmic Electric Fields and Phosphorylated Messenger Proteins Optimize Information Flow in Cells

Abstract

BackgroundNormal cell function requires timely and accurate transmission of information from receptors on the cell membrane (CM) to the nucleus. Movement of messenger proteins in the cytoplasm is thought to be dependent on random walk. However, Brownian motion will disperse messenger proteins throughout the cytosol resulting in slow and highly variable transit times. We propose that a critical component of information transfer is an intracellular electric field generated by distribution of charge on the nuclear membrane (NM). While the latter has been demonstrated experimentally for decades, the role of the consequent electric field has been assumed to be minimal due to a Debye length of about 1 nanometer that results from screening by intracellular Cl− and K+. We propose inclusion of these inorganic ions in the Debye-Huckel equation is incorrect because nuclear pores allow transit through the membrane at a rate far faster than the time to thermodynamic equilibrium. In our model, only the charged, mobile messenger proteins contribute to the Debye length.FindingsUsing this revised model and published data, we estimate the NM possesses a Debye-Huckel length of a few microns and find this is consistent with recent measurement using intracellular nano-voltmeters. We demonstrate the field will accelerate isolated messenger proteins toward the nucleus through Coulomb interactions with negative charges added by phosphorylation. We calculate transit times as short as 0.01 sec. When large numbers of phosphorylated messenger proteins are generated by increasing concentrations of extracellular ligands, we demonstrate they generate a self-screening environment that regionally attenuates the cytoplasmic field, slowing movement but permitting greater cross talk among pathways. Preliminary experimental results with phosphorylated RAF are consistent with model predictions.ConclusionThis work demonstrates that previously unrecognized Coulomb interactions between phosphorylated messenger proteins and intracellular electric fields will optimize information transfer from the CM to the NM in cells.

Estimating a Repeatable Statistical Law by Requiring Its Stability During Observation

“…This is found to hold, e.g., for all shift-invariant phenomena that ultimately have a physical basis. Principle (1) has been applied in [4][5][6][7][8][9][10] to derive wave equations of quantum mechanics, basic thermodynamics and modern cell biology. Also derived have been the phenomena of statistical physics and other sciences [6,[11][12][13][14][15][16][17][18][19].…”

Cell Development Pathways Follow from a Principle of Extreme Fisher Information

“…We proposed [5] that for functioning eukaryotes, with their intrinsically higher requirements of order and complexity, the extreme information state should be a maximum. Here we quantify its value.…”

“…However, this would disperse the proteins throughout the cell so that information about their point of origin on CM would be lost, counter to our requirement of information maximization. We previously proposed [5] that efficient movement of proteins toward the NM will occur if random diffusion is replaced by highly directed (biased) random walk. This is accomplished by the presence of an intracellular electric field set up by the nucleus and possible mitochondria.…”

“…We propose that these charges enhance existing Coulomb interactions with the intracellular field and that these forces enhance the directed nature of the protein movement toward the NM. The theoretical and experimental details of this model are treated elsewhere [5].…”

“…(Note: In this paper "cells" mean "eukaryotes" unless otherwise described.) In prior work [1][2][3][4][5] we have demonstrated that a stable highly ordered system, including functioning cells and multicellular tissue, must maintain a state of extreme Fisher information, 2 0 ( / ) ( ) ≡ = = ∫ dp dx I I x dx p extremum,…”