Robust replication initiation from coupled homeostatic mechanisms.

The bacterium Escherichia coli initiates replication once per cell cycle at a precise volume per origin and adds an on average constant volume between successive initiation events, independent of the initiation size. Yet, a molecular model that can explain these observations has been lacking. Experiments indicate that E. coli controls replication initiation via titration and activation of the initiator protein DnaA. Here, we study by mathematical modelling how these two mechanisms interact to generate robust replication-initiation cycles. We first show that a mechanism solely based on titration generates stable replication cycles at low growth rates, but inevitably causes premature reinitiation events at higher growth rates. In this regime, the DnaA activation switch becomes essential for stable replication initiation. Conversely, while the activation switch alone yields robust rhythms at high growth rates, titration can strongly enhance the stability of the switch at low growth rates. Our analysis thus predicts that both mechanisms together drive robust replication cycles at all growth rates. In addition, it reveals how an origin-density sensor yields adder correlations.

Towards a synthetic cell cycle.

Recent developments in synthetic biology may bring the bottom-up generation of a synthetic cell within reach. A key feature of a living synthetic cell is a functional cell cycle, in which DNA replication and segregation as well as cell growth and division are well integrated. Here, we describe different approaches to recreate these processes in a synthetic cell, based on natural systems and/or synthetic alternatives. Although some individual machineries have recently been established, their integration and control in a synthetic cell cycle remain to be addressed. In this Perspective, we discuss potential paths towards an integrated synthetic cell cycle.

Nanodomains in Biomembranes with Recycling.

Cell membranes are out of thermodynamic equilibrium notably because of membrane recycling, i.e., active exchange of material with the cytosol. We propose an analytically tractable model of biomembrane predicting the effects of recycling on the size of protein nanodomains also called protein clusters. The model includes a short-range attraction between proteins and a weaker long-range repulsion which ensures the existence of so-called cluster phases in equilibrium, where monomeric proteins coexist with finite-size domains. Our main finding is that, when taking recycling into account, the typical cluster size at steady state increases logarithmically with the recycling rate at fixed protein concentration. Using physically realistic model parameters, the predicted 2-fold increase due to recycling in living cells is most likely experimentally measurable with the help of super-resolution microscopy.