Protein condensates that form by undergoing liquid-liquid phase separation will show changes in their rheological properties with time, a process known as aging. Jawerth et al. used laser tweezer–based active and microbead-based passive rheology to characterize the time-dependent material properties of protein condensates (see the Perspective by Zhang). They found that condensate aging is not gelation of the condensates, but rather a changing viscoelastic Maxwell liquid with a viscosity that strongly increases with age, whereas the elastic modulus stays the same. Science , this issue p. ; see also p.  Protein condensates are complex fluids that can change their material properties with time. However, an appropriate rheological description of these fluids remains missing. We characterize the time-dependent material properties of in vitro protein condensates using laser tweezer–based active and microbead-based passive rheology. For different proteins, the condensates behave at all ages as viscoelastic Maxwell fluids. Their viscosity strongly increases with age while their elastic modulus varies weakly. No significant differences in structure were seen by electron microscopy at early and late ages. We conclude that protein condensates can be soft glassy materials that we call Maxwell glasses with age-dependent material properties. We discuss possible advantages of glassy behavior for modulation of cellular biochemistry. : /lookup/doi/10.1126/science.aaw4951 : /lookup/doi/10.1126/science.abe9745
In recent years, quantum fluids have been studied largely in gaseous form, such as the Bose-Einstein condensates (BECs) of alkali atoms and related species. Quantum liquids, other than liquid helium, have been comparatively more difficult to come by. Cabrera et al. combined two BECs and manipulated the atomic interactions to create droplets of a quantum liquid (see the Perspective by Ferrier-Barbut and Pfau). Because the interactions were not directional, the droplets had a roughly round shape. The simplicity of this dilute system makes it amenable to theoretical modeling, enabling a better understanding of quantum fluids.
There is increasing interest in the function of phase-separated biomolecular condensates in cells because of their distinct properties and expanding roles in important biological processes. Klein et al. considered the fate of small-molecule therapeutics in the context of nuclear condensates (see the Perspective by Viny and Levine). They show that certain antineoplastic drugs have physicochemical properties that cause them to concentrate preferentially in condensates, both in vitro and in cancer cells. This property influences drug activity, and protein mutations that alter condensate formation can lead to drug resistance. Optimizing condensate partitioning may be valuable in developing improved therapeutics.
Here, we show that the prion domain of Sup35 drives the reversible phase separation of the translation termination factor into biomolecular condensates. These condensates are distinct and different from fibrillar amyloid-like prion particles. Combining genetic analysis in cells with in vitro reconstitution protein biochemistry and quantitative biophysical methods, we demonstrate that Sup35 condensates form by pH-induced liquid-like phase separation as a response to sudden stress. The condensates are liquid-like initially but subsequently solidify to form protective protein gels. Cryo–electron tomography demonstrates that these gel-like condensates consist of cross-linked Sup35 molecules forming a porous meshwork.
Many mysteries remain about the eukaryotic nucleus. In the past decade, much has been discovered anew about the three-dimensional (3D) organization of the nucleus and the dynamic interactions therein that influence cellular function. Studies have uncovered the critical roles that topologic structure, histone modifications, and DNA modifications play in regulating transcription. By contrast, the understanding of interactions among proteins, RNA, and chromatin in macromolecular assemblies is less developed. These condensates are the molecular basis for discrete nuclear spatial organization of active and repressive chromatin as well as distinct nuclear structures such as the nucleolus (1, 2).