Integrated simulations of active emulsions in complex environments

Introduction

Biological cells consist of a myriad of interacting biomolecules that collectively arrange in stable structures. For example, molecules undergo phase separation to form so-called biomolecular condensates. 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.

Challenges in Understanding Condensate Dynamics

Some challenges in understanding condensate dynamics are:

• Cells are heterogeneous.
• Cells have complex material properties.
• Cells exhibit significant thermal fluctuations.

Biological cells are also alive and use fuel molecules to control processes actively. I recently showed that active chemical reactions could generally affect the dynamics of droplets. However, it is unclear how such active droplets behave in the complex environments inside cells.

Project Overview

EmulSim will study how cells control biomolecular condensates and provide a novel integrated simulation method incorporating relevant processes on all length scales.

Scale of Individual Droplets

On the scale of individual droplets, I will investigate the influence of:

1. Driven reactions
2. Elastic material properties of droplets

Cellular Scale

On the cellular scale, I will study the effect of:

• The elastic cytoskeleton
• The presence of multiple compartments

Model Development

For each of these processes, I will derive experimentally verified models using examples of relevant biological processes, including:

• Cell division
• Chromatin organization
• Signaling

Combining the physical theories for these critical processes will culminate in an agent-based model describing a collection of droplets, ultimately also including number fluctuations.

Conclusion

This novel simulation framework will model biomolecular condensates in their cellular environment. Taken together, EmulSim will propel our understanding of biomolecular condensates and lay the ground for the development of novel therapies in medicine.