Biomolecular condensates

Condensates that form via passive mechanisms are inherently difficult to control. To achieve control of condensate size and positioning, cells can utilise active (i.e. energy consuming) chemical reactions to drive the conversion of precursor molecules into a corresponding self-assembling form. When condensate function includes the transduction of mechanical forces, condensates must exhibit solid-like mechanical strength, without compromising their liquid-like ability to form and grow rapidly. 

In collaboration with the groups of Sebastian Aland and Alex Dammermann, we recently showed that the combination of active material incorporation and a viscoelastic rheology allows the precise and controlled formation of mechanically strong condensates within the cell (see here). As an example, we compare our theoretical predictions with experimental data for centrosomes, which are membrane-less organelles that form rapidly during mitosis and physically segregate chromosomes during cell division, identifying constraints on the material parameters for which centrosomes are viable.

Although the fundamental principles of condensate formation are relatively well understood, classical descriptions of droplet dynamics based on passive liquid-liquid phase separation are insufficient to capture the incredible complexity within living cells. For example, the inherent diversity of individual biomolecules typically leads to complex material properties such as viscoelasticity. Further, condensates do not exist in isolation within the cell, instead wetting solid-like structures such as the cytoskeleton and lipid membranes. Finally, biological cells fundamentally exist out of thermodynamic equilibrium, allowing cells to use active processes to achieve control over condensate formation and growth.

In our recent review article, we highlight how cells can use soft matter physics to regulate the spatiotemporal organisation of condensates, controlling their nucleation, growth, position, and count.