The basis of synchronization by repetitive dilution of a growing culture

Cultures of Escherichia coli have been synchronized by periodic dilution with fresh growth medium in the laboratory of Francois Kepes. When diluted by a large factor into complete test medium, the treated cultures undergo up to 12 synchronous divisions. This long term synchrony must result from an adjustment process during the periodic dilution procedure so that all cells have nearly identical biochemical properties. Robert Pritchard (University of Leicester, personal communication) suggested that this phasing would happen if the uptake of a critical nutrient was limited by the surface area of the cell during a portion of the dilution cycle. If his suggestion is valid, a general method for synchronization of almost any organism that grows exponentially and divides by binary fission into equal sized daughters should be achievable. A computer program was devised to simulate the growth of an initially asynchronous culture under periodic dilution with medium containing a single limiting nutrient. Various models of cell shape and growth were tested along with various models for the growth-limiting substrate uptake.