Growth kinetics of bacterial pili from pairwise pilin association rates.

Bacterial pilogenesis is a remarkable example of biological non-templated self-assembly where a small number of different building blocks are arranged in a specific order resulting in a macroscopic hair-like fiber containing up to thousands copies of protein subunits. A number of advanced experimental techniques have been used to understand pilus growth. While details such as the conformation of the protein building blocks before and after the elementary polymerization step have enhanced our understanding of this mechanism, such information does not explain the high efficiency of this growth process. In this study, we focused on the growth of the Escherichia coli P-pilus, which is formed by the assembly of six subunits, structurally similar incomplete Ig-like domains. These subunits undergo polymerization through fold complementation by the donation of a β-sheet strand in a specific conserved order. All pairwise rates of association of the individual subunits with the corresponding β-sheet donor strand peptides have been previously determined through non-covalent mass-spectrometry. Here we use computational simulations to determine donor-strand exchange rates and subunit concentrations necessary to warrant the growth of pili showing similar lengths and subunit orders to those observed in vivo. Our findings confirm that additional factors must be involved in the modulation of the donor-strand exchange rate and/or pilin subunit concentration at the usher must be important for the precise ordering and rapid polymerization rates observed in vivo.