J. theor. Biol. (1992) 154, 91-107 Phospholipid Domains Determine the Spatial Organization of the Escherichia coil Cell Cycle: the Membrane Tectonics Model VIC NORRIS Department of Genetics, University of Leicester, Leicester LE1 7RH, U.K. (Received on 16 January 1991, Accepted in revised form on 12 September 1991) Escherichia coli normally divides at its equator between segregated nucleoids. Such division is inhibited during perturbations of chromosome replication (even in the absence of inducible division inhibitors); eventually, division resumes at sites which are not at this equator. Escherichia coli will also divide at its poles to generate minicells following overproduction of the FtsZ or MinE proteins. The mechanisms underlying the division inhibition and the positioning of the division sites are unknown. In the membrane tectonics model, I propose that the formation of phos- pholipid domains within the cytoplasmic membrane positions division sites. The particular phospholipid composition of a domain attracts particular proteins and determines their activity; conversely, particular proteins change the composition of domains. Principally via such proteins, the interaction of the chromosome with the membrane creates a chromosomal domain. The development of chromosomal domains during replication and nucleoid formation contributes to the formation and positioning of a septal domain between them. During septation (cell division), this septal domain matures into a polar domain. Each domain attracts and activates different enzymes. The septal domain attracts and activates enzymes necessary for septation. Preventing the formation of the septal domain by preventing chromosome replication prevents normal division. Altering the composition of the polar domain may allow septation enzymes to function there and generate minicells. A corollary of the model explains how the formation of an origin domain by the attachment of hemi-methylated origin DNA to the membrane may underlie the creation and migra- tion of structures within the envelope, the periseptal annuli. Introduction During the cell cycle of Escherichia coli cells normally divide at the equator between the segregated nucleoids. This process is tightly controlled and septum formation is timed and positioned such that daughter cells are of similar sizes and few DNA-less cells are formed (Jaff6 et al., 1986). Although some components of the mechanism responsible for this control have been elucidated, the mechanism itself remains obscure. In E. coli, the position and development of the constriction site is related to the position and activity of the chromosomes. Perturbations of chromosome replication result in an inhibition of cell division due to the synthesis of a division inhibitor, SfiA (Huisman & D'Ari, 1981 ; Little & Mount, 1982). In the absence of SfiA, cell division is still inhibited by a "second mechanism" (Huisman et al., 1980; Burton & Holland, 1983). The nature of this second inhibitory mechanism is unknown. In 91 0022-5193/92/010091 + 17 $03.00/0 © 1992 Academic Press Limited