![]() coli generates substantial phenotypic diversity ( Godin et al., 2010 Wang et al., 2010 Kiviet et al., 2014 Osella et al., 2014 Taheri-Araghi et al., 2015) with cell division playing the key role. This fitted with the idea that the laws underlying cell growth – and, in particular, those directly relevant to the cell cycle – could be found not by studying single cells but rather by studying cells as an aggregate ( Cooper, 2006). In non-differentiating bacteria such as Escherichia coli, the cell cycle was long considered to have only the function of replicating the hereditary material and distributing it into two cells that would be effectively identical unless driven down the path of differentiation. The above problems are intimately related to the cell cycle. This is particularly serious because patterns of connectivity are often claimed to define pretty well everything – as testified by the claims of universality made for self-organized criticality ( Bak, 1996) and small world networks ( Watts and Strogatz, 1999) – so that a bacterium that continued to grow would eventually lose its identity. More generally still, bacteria – like all living objects – risk losing the connectivity between their constituents as they get bigger ( Norris, 2015). More generally, bacteria must have found ways to avoid incoherence at the level of both the individual cell and the population so as to be able to not only grow but also survive (arguably, the more important of the two behaviors since a dead cell can never grow) in what we have called ‘Life on the Scales’ ( Norris and Amar, 2012a). These problems include DNA becoming a limiting factor (thereby disrupting patterns of expression and preventing exponential growth), positive feedback (thereby leading to a single phenotype), over-reliance on fragile, non-equilibrium ( NE) structures such as those created by the coupling of transcription, translation (thereby making the cell vulnerable to changes in its environment), and unbalanced production of RNA, protein and lipid ( Norris, 2011). The very fact of growing is a source of many serious problems that bacteria somehow have to solve. The solution is the use of a range of mechanisms ranging from hyperstructure dynamics to the cell cycle itself. This means that the selection of an active subset of a specific size and composition must be done so as to generate both a coherent cell state, in which the cell’s contents work together harmoniously, and a coherent sequence of cell states, each coherent with respect to itself and to an unpredictable environment. A third idea from artificial intelligence – Competitive Coherence – is that a cell selects the active subset of elements that actively determine its phenotype from a much larger set of available elements. The solution is that the cell cycle generates daughter cells with different phenotypes based on sufficiently complex equilibrium ( E) and non-equilibrium ( NE) cellular compounds and structures appropriate for survival and growth, respectively, alias ‘hyperstructures.’ The corollary is that the cell senses both the quantity of E material and the intensity of use of NE material and then uses this information to trigger the cell cycle. This means that it has learnt to reconcile the opposing constraints that these strategies impose. A second idea from phenotypic diversity – Life on the Scales of Equilibria – is that a bacterium must find strategies that allow it to both survive and grow. ![]() The corollary is that the cell senses decreasing cellular connectivity and uses this information to trigger division. The solution is division which restores connectivity. ![]() This means that if the growing cell were just to get bigger the average connectivity between its constituents per unit mass – its cellular connectivity – would decrease and the cell would lose its identity. One idea from the origins of life – Life as independent of its constituents – is that a living entity like a cell is a particular pattern of connectivity between its constituents. The problem of not only how but also why cells divide can be tackled using recent ideas. ![]() Laboratory of Microbiology Signals and Microenvironment, Theoretical Biology Unit, University of Rouen, Mont Saint Aignan, France.
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