University of Cambridge
Zooming into biomolecular condensates
The interior of cells contains numerous components that need to be carefully organized in space to fulfill a wide range of biological functions. The most widespread form of intracellular compartments completely lack membranes. In the place of membranes, these compartments—so called biomolecular condensates—are sustained and segregated in space by the physical chemistry of liquid–liquid phase separation, analogous to how oil drops separate when dispersed in water. Complementary to experiments, molecular modeling and simulations have surfaced as powerful tools for providing us with the missing close-up views to understand the modulation of biomolecular phase behavior.
In this seminar, I will describe the use of atomistic and coarse-grained simulations to shed light on the molecular grammar underlying phase separation and account for salt-mediated reentrant phase transitions observed experimentally. I will explain how our simulations reveal distinctly different molecular driving forces stabilizing condensates in the low and high-salt regime, highlighting that the molecular grammar is not only dictated by the amino acid sequence but also crucially altered by the condensate environment. I will also discuss current efforts at developing transferable computer models that can predict biomolecular phase boundaries with quantitative accuracy. Finally, I will outline how we can advance the state-of-the-art to not only understand phase separation at the molecular level but to tune and control it on demand.