Séminaire externe - Enrico Lavagna (CBS - Montpellier)

Abstract:

Cellular condensates are membrane-less organelles that play key roles in many cellular processes across all forms of life. Condensates are composed of proteins and nucleic acids bound by weak interactions and mostly display liquid-like behavior, prompting researchers to study their features in the framework of liquid-liquid phase separation. In recent years, however, it became apparent that phase separation alone cannot explain their real-world complexity: assembly and dissolution are quick and time-sensitive, while cellular signaling finely controls their size and number. Which molecular processes allow the cell to regulate condensate activity? Among other known mechanisms, controlled post-translational modifications of scaffold proteins influence their condensation properties. 

We present an in silico approach to investigate the enzymatic regulation of condensates. In our model, proteins change their interaction strength upon reactions, which occur upon contact with explicit enzymes. We show how enzyme concentration and activity influence the phase diagram, highlighting the role of the condensate interface and the interplay between the protein modification strength and actual reaction rates. We can observe reaction fluxes and other effects typical of out-of-equilibrium systems. Moreover, simulations show that condensates promote a reaction-rate steepening effect akin to ultrasensitivity. This simple but novel approach overcomes the limitations of continuum theoretical approaches and can be used to complement experimental data obtained in vitro or in vivo.