Alternative models for cell fate selection in a population of genetically identical cells. (A) Variation during infection (for example, spontaneous chemical kinetic noise) leads to qualitative differences in cell fate. (B) Variation in the physical state of individual cells before infection predetermines cell fate.

Genetically identical cells can be separated into many fractions. Asynchronous cultures of stationary phase E. coli MG1655 were sorted by using counterflow centrifugal elutriation (see Experimental Procedures). (A–C) The distribution of cell volumes obtained by microscopy (n > 500) and electronic (n > 10,000) measurements are shown for representative small (A) and large (B) fractions, as well as for the starting asynchronous population (C). (See Fig. S4 for additional fractions.) CoV, coefficient of variation. (D–F) Representative phase contrast pictures are shown to the right of the corresponding volume distributions. (Scale bars: 5 μm.)

Variation in developmental outcome is a function of physical variation that exists before infection. Independent measurements of the fraction of lytic events and lysogeny as a function of the mean cell volume for different cell fractions. Developmental outcome is expressed as a percentage of an independent measure of the total number of infected cells for each fraction. Circles, triangles, and squares depict fractions collected from 3 independent experiments. The 3 starting asynchronous (unfractionated) cultures are also shown († near data points). Error bars indicate the Poisson standard error of the mean from plating. Dashed lines indicate linear regression lines for percentage lysis and lysogeny and the sum of lytic events and lysogens.

Cell fate selection in individual cells. Images from time-lapse movies of exponentially growing JW4132 (hflK⁻) cells infected at a phage-to-cell ratio of ≈1:30 with a lambda strain carrying a fluorescent reporter expression cassette. Numbers indicate the number of minutes at which the images were taken after the start of each movie. (Upper) Two neighboring cells are infected, each presumably at a multiplicity of one, and both cells turn green over time. The upper-right infected cell is larger and near the end of its cell division cycle, as indicated by the presence of a membrane invagination (developing septum) at mid-cell. This cell lyses between 132 and 177 min. The lower-left infected cell, which is presumably the product of a recent cell division event and is relatively small, continues to progress through a typical cell division cycle. The infected cell was presumably lysogenized by lambda as it survives the infection, producing viable progeny which also divide between 461 and 520 min. (Lower) An infected cell produces daughter cells with apparently distinct fates: the rightmost daughter lyses between 527 and 559 min, whereas the leftmost daughter divides ≈372 min, producing progeny which themselves divide ≈714 min.

Extrinsic variation helps determine developmental outcome of single infected cells. Probability of lysogeny as a function of the volume of individual MG1655 (hflK⁺) grown to stationary phase (A) or JW4132 (hflK⁻) grown to exponential phase (B). The numbers in parentheses represent the number of lysogens over the total number of infected cells within each volume bin (excluding “mixed fate” cells). The dashed lines correspond to the average percentage lysogeny in each condition.