Resolving non-equilibrium biomolecular transitions with coherent X-rays

The environment inside a cell is highly crowded, which can alter drastically the behaviour of macromolecular in solution.

Such crowding effects can induce the formation of biomolecular condensates, which are liquid-like membrane-less droplets.

Despite the general occurrence of biomolecular condensates, the physical mechanism governing the early stages of their formation is still debated.

Here, a novel approach is proposed for probing and controlling the early stages of biomolecular condensation using microdroplet reactors.

The proposed research aims to provide new exciting experimental insights towards a general framework that predicts and explains the phase behavior of macromolecules.

The project´s timing is ideal as it utilizes diffraction-limited storage rings (DLSRs) and X-ray free electron lasers (XFELs), which are supported by the Swedish Research Council.

The strength of the proposed coherent X-ray techniques is that they allow to capture non-equilibrium structural dynamics at unprecedented resolution, reaching protein molecular level sensitivity and sub-microsecond timescales.

The proposed investigations not only train new scientists but also contribute to Sweden´s long-term competitiveness in X-ray science.

Resolving and controlling the biomolecular condensation mechanism is essential for understanding cellular function, as well as for treating aggregation diseases and facilitate the formulation of future protein-based drugs and materials.