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Robert A. Gatenby and B. Roy Frieden
Background: In a normally developing eukaryote, information arrives at the cell membrane in the form of a ligand that binds to a protein receptor. This initiates a cascade of biochemical events causing one or more proteins to subsequently traverse the cell cytoplasm to the nucleus. This defines a communication channel. What does it accomplish? Method: The protein traversals transfer to the nucleus maximum Fisher information about the spatial and temporal coordinates of the ligand binding sites. This hypothesis implies a cell model of fast, largely-directed, protein movement dominated by Coulomb interaction with intracellular electric fields. It makes the following predictions: (1) Very high intracellular electric field strengths, typically tens of millions of volts/meter (2) A central role for negative charges added to proteins by phosphorylation, in promoting their Coulomb force-dominated motion toward the nucleus; (3) The dominance of protein pathways consisting of from 1-4 proteins, e.g. the RAF, RAS and MEK pathways; (4) A predicted fast response (2,800 proteins/ ms ) of cells to sudden trauma such as wounds; (5) A predicted 4nm size (9) for the EGFR protein. (6) Logic mechanisms in the nucleus for optimally deconvolving spatial and temporal binding site values from the inflowing messenger proteins. Results: Predictions (1-5) are supported by laboratory observations. Conclusions: Living systems achieve stably ordered and complex states by maintaining extreme levels of Fisher information. The attained order values increase from cancers to prokaryotes to eukaryotes to multicellular organisms. In eukaryotes this fosters maximally high protein flux rates at the nucleus which, in turn, optimize wired-in intranuclear logic mechanisms for processing this, and other, temporal and spatial information.