Biological cells consist of a myriad of interacting biomolecules that collectively arrange in stable structures. Understanding the physical principles of such spatiotemporal control is crucial for curing diseases and leveraging similar principles for designing synthetic systems. The project EmulSim focus on the physical process of phase separation, which describes how molecular interactions lead to the spontaneous formation of droplets, known as biomolecular condensates, in cells. We now know that malfunctioning condensates can cause diseases like Alzheimer’s, Parkinson’s, and cancer. Yet, we do not understand how condensates become malfunctioning and how healthy cells control them. Some challenges in understanding condensate dynamics are that cells are heterogeneous, have complex material properties, and exhibit significant thermal fluctuations. Biological cells are also alive and use fuel molecules to control processes actively. However, it is unclear how such active droplets behave in the complex environments inside cells. The main objective of EmulSim is to study the effect of multiple physical processes onto biomolecular condensates to obtain a clearer picture of how cells control them, what might go wrong during diseases, and how we might be able to fix this.
Specifically, the objective of EmulSim is to provide a novel integrated simulation method incorporating relevant processes on all length scales. On the scale of individual droplets, it will incorporate the influence of driven reactions and elastic material properties of droplets. On the cellular scale, the effect of the elastic cytoskeleton and the presence of multiple compartments will be crucial. For each of these processes, we derive experimentally verified models using examples of relevant biological processes, including cell division, chromatin organization, and signaling. Combining the physical theories for these critical processes will culminate in an agent-based model describing a collection of droplets, ultimately also including thermal fluctuations. This novel simulation framework will model biomolecular condensates in their cellular environment taking key physical processes into account and providing a platform for future research and extensions to include additional processes. Taken together, the objective of EmulSim is to propel our understanding of biomolecular condensates and lay the ground for the development of novel therapies in medicine.
