Biomolecular condensates and intrinsically disordered proteins

5 problems

• Mechanism of liquid-to-solid aging of condensates

  Open

  Some protein droplets slowly harden from liquid to gel or solid over hours, and in disease they can turn into fibers. What molecular process drives this hardening and sets its rate is unknown.

• Do condensates perform functions beyond molecular binding?

  Contested

  Many proteins form droplets in cells, but whether the droplet itself does a job, or forms only because the proteins happen to be sticky, is often unknown. Separating the two requires changing droplet formation without changing the proteins' other properties.

• Decisive test that a cellular body forms by phase separation

  Contested

  Many cellular structures look like droplets, but similar clusters can form by simple binding to a scaffold without any phase transition. A reliable experimental signature that tells them apart is needed.

• Predict condensate phase diagrams from protein sequence

  Partially resolved

  A disordered protein's amino-acid sequence decides at what concentration it forms droplets. A method that predicts this concentration from sequence, across salt and temperature, would connect sequence to physics directly.

• How cells control the size and number of condensates

  Contested

  Ordinary droplets merge, and large ones grow at the expense of small ones until one big drop remains. Cells keep many small condensates of controlled size, and which physics stops the merging is disputed.