On the origins of a crowded cytoplasm.

Contemporary cells show a highly crowded macromolecular content, the processes which originated this state being largely unknown. We propose that a driving force leading to the crowded cellular state could be the increase in growth rate produced by an enhanced cytoplasmic protein concentration. Briefly, in a diluted scenario, an increase in protein concentration has two opposing effects on growth rate. The favorable effect is the increase in the activity per unit volume of the component proteins and the disadvantageous effect is the concomitant increase in the protein mass per unit volume which has to be produced. In this work we show that the first effect is quantitatively more important, resulting in an overall increase in growth rate. This result was obtained with a model of E. coli and using nonmechanistic physiological arguments. The proposed driving force operates even at low protein concentrations, where the nonspecific interactions of macromolecular crowding are not significant, and could be as ancient as the first protocells. Experimental measurement of this cytoplasmic protein concentration effect in present organisms is hindered by the prevailing nonspecific interactions, product of long-term evolution. However, chemical/biochemical systems, built up to mimic properties of living cells, could be an adequate tool to test this effect.