Co-condensation of proteins with single- and double-stranded DNA

Biomolecular condensates provide distinct compartments that can localize and organize biochemistry inside cells. Recent evidence suggests that condensate formation is prevalent in the cell nucleus. To understand how different components of the nucleus interact during condensate formation is an important challenge. In particular, the physics of co-condensation of proteins together with nucleic acids remains elusive. Here we use optical tweezers to study how the prototypical prion-like protein Fused-in-Sarcoma (FUS) forms liquid-like assemblies in vitro, by co-condensing together with individual DNA molecules. Through progressive force induced peeling of dsDNA, buffer exchange, and force measurements, we show that FUS adsorbing in a single layer on DNA effectively generates a sticky FUS-DNA polymer that can collapse to form a liquid-like FUS-DNA co-condensate. Condensation occurs at constant DNA tension for double-stranded DNA, which is a signature of phase separation. We suggest that co-condensation mediated by protein monolayer adsorption on nucleic acids is an important mechanism for intracellular compartmentalization.

Automated summary

This study investigated the mechanism of how the FUS protein forms liquid-like assemblies by co-condensing with DNA molecules in vitro. It was found that the protein could adsorb onto DNA to generate a sticky FUS-DNA polymer, which then collapsed to form a liquid-like FUS-DNA co-condensate. The co-condensation mechanism mediated by protein adsorption on nucleic acids is suggested to be important for intracellular compartmentalization.