Universiteit Leiden

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Louise Jawerth Lab

Protein condensates as Materials

We have recently discovered that there are biological proteins that phase separate out of solution much the way oil will de-mix from water (see movie). These form dense, liquid-like phases called protein condensates.

So far, this appears to be a very important and general strategy utilized by cells to form compartments with material properties tuned to their specific function. To first approximation, we can understand this process using physical principles developed to understand synthetic polymers.

Phase Separated Droplets
Phase Separated Droplets (click for Video)

However, unlike synthetic polymers, biological proteins have specific and intricate amino acid sequences. First, this gives rise to an incredibly diverse set of material behaviors which we are only beginning to discover. These include aging similar to glasses (see Movie 2), ultra-low surface tensions, spatially localized wetting, growth into well-ordered fibers, as well as active processes.

Second, inside of cells, we expect these properties to be quickly tuned by cells through modifications of the protein sequence (eg. phosphorylation). 

One of the research directions in the lab is to study the material nature of these protein condensates and uncover the physical principles which govern them.

Oftentimes, our work requires building new tools that can quantitatively measure and manipulate these materials on the lengthscale of microns. We also rely heavily on quantitative image processing.

We use this information to build a conceptual framework from which we understand how microscopic processes lead to bulk behaviors. Moreover, we work in close collaboration with theory colleagues to quickly turn this conceptual framework into a rigorous theoretical understanding. 

Green monster (click for video)
Green monster (click for video)

Movie 2 (Movies and figures from Jawerth et al Science 2020). Protein condensates exhibit time dependent properties. In this movie we see protein condensates (in green) shortly after formation. Initially their coalescence is fast suggesting quick internal dynamics. Over time, however, the coalescence slows. This indicates that the material has age dependent properties. By following the thermal diffusion of small markers (in magenta) we are also able to estimate the material properties of the droplets as they age. 

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