Equilibrium melting probabilities of a DNA molecule with a defect: An exact solution of the Poland-Scheraga model.

In this study we derive analytically the equilibrium melting probabilities for basepairs of a DNA molecule with a defect site. We assume that the defect is characterized by a change in the Watson-Crick basepair energy of the defect basepair, and in the associated two stacking energies for the defect, as compared to the remaining parts of the DNA. The defect site could, for instance, occur due to DNA basepair mismatching, cross-linking, or by the chemical modifications when attaching fluorescent labels, such as fluorescent-quencher pairs, to DNA. Our exact solution of the Poland-Scheraga model for DNA melting provides the probability that the labeled basepair, and its neighbors, are open at different temperatures. Our work is of direct importance, for instance, for studies where fluorophore-quencher pairs are used for studying single basepair fluctuations of designed DNA molecules.

Analytical cell size distribution: lineage-population bias and parameter inference.

We derive analytical steady-state cell size distributions for size-controlled cells in single-lineage experiments, such as the mother machine, which are fundamentally different from batch cultures where populations of cells grow freely. For exponential single-cell growth, characterizing most bacteria, the lineage-population bias is obtained explicitly. In addition, if volume is evenly split between the daughter cells at division, we show that cells are on average smaller in populations than in lineages. For more general power-law growth rates and deterministic volume partitioning, both symmetric and asymmetric, we derive the exact lineage distribution. This solution is in good agreement with Escherichia coli mother machine data and can be used to infer cell cycle parameters such as the strength of the size control and the asymmetry of the division. When introducing stochastic volume partitioning, we derive the large-size and small-size tails of the lineage distribution and show that the lineage-population bias only depends on the single-cell growth rate. These asymptotic behaviours are extended to the adder model of cell size control. When considering noisy single-cell growth rate, we derive the large-size lineage and population distributions. Finally, we show that introducing noise, either on the volume partitioning or on the single-cell growth rate, can cancel the lineage-population bias.

Fluctuation relations and fitness landscapes of growing cell populations.

We construct a pathwise formulation of a growing population of cells, based on two different samplings of lineages within the population, namely the forward and backward samplings. We show that a general symmetry relation, called fluctuation relation relates these two samplings, independently of the model used to generate divisions and growth in the cell population. These relations lead to estimators of the population growth rate, which can be very efficient as we demonstrate by an analysis of a set of mother machine data. These fluctuation relations lead to general and important inequalities between the mean number of divisions and the doubling time of the population. We also study the fitness landscape, a concept based on the two samplings mentioned above, which quantifies the correlations between a phenotypic trait of interest and the number of divisions. We obtain explicit results when the trait is the age or the size, for age and size-controlled models.

Linking lineage and population observables in biological branching processes.

Using a population dynamics inspired by an ensemble of growing cells, a set of fluctuation theorems linking observables measured at the lineage and population levels is derived. One of these relations implies specific inequalities comparing the population doubling time with the mean generation time at the lineage or population levels. While these inequalities have been derived before for age-controlled models with negligible mother-daughter correlations, we show that they also hold for a broad class of size-controlled models. We discuss the implications of this result for the interpretation of a recent experiment in which the growth of bacteria strains has been probed at the single-cell level.