Bistability, hysteresis and stochastic switching in the <i>lac</i> system.

<p>(A) Single <i>lacI</i> A₉ cells in minimal succinate media ± maintenance TMG were grown into microcolonies in a microfluidic flow chamber (approximately 100 cell divisions per microcolony originating from a single cell; number of divisions equals final number of cells in a microcolony minus 1). Comparison of bright field images (panel series on the left) with GFP fluorescence images (panel series on the right) allows clear distinction between OFF and ON cells in the microcolony. (I) panels show microcolonies that arose from single ON cells that were subsequently grown in the presence of maintenance level TMG; (II) panels show mirocolonies that arose from single OFF cells that were subsequently grown in the presence of maintenance level TMG; (III) panels show mirocolonies that arose from single OFF and single ON cells that were subsequently grown in the presence of maintenance level TMG; (IV) panels show a mirocolony that arose from ON cells that were subsequently grown in the absence of maintenance level TMG. Exposure to fluorescence illumination was 3000 ms. (B) A single <i>lacI</i> A₉ cell in minimal succinate media+maintenance TMG was grown into a microcolony in a microfluidic flow chamber and monitored by time-lapse fluorescence microscopy. Presented here are four still images from a full time series of images (available as <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003595#pgen.1003595.s007" target="_blank">Movie S1</a>; images shown correspond to frames 25, 28, 30, 39). Comparison of bright field images (panel series on the left) with GFP fluorescence images (panel series on the right) allows distinction between OFF and ON cells in the microcolony. (I) all cells in the microcolony are OFF (100 ms exposure to fluorescence illumination); (II) a recently divided cell is just becoming ON indicated by the arrow (100 ms exposure to fluorescence illumination); (III) the now separated cells have become ON (100 ms exposure to fluorescence illumination); (IV) further cell division has occurred in the microcolony creating one lineage of ON cells amongst many other lineages of OFF cells (3000 ms exposure to fluorescence illumination). The 100 ms exposure time images were over-exposed using the ColorSync Utility to observe the faint fluorescence signal.