In the last decade, scientists have discovered that in addition to the well-known membrane-enclosed organelles, cells also contain many membrane-less organelles called “biomolecular condensates.” Biomolecular condensates comprise proteins and nucleic acids that come together through weak, temporary interactions, forming dynamic and flexible structures that can change and adapt as needed. These structures are crucial for the proper functioning of cells, helping to organize and compartmentalize different cellular processes.

The Biological condensates special issue published in Biophysical Journal explores various aspects of these condensates through different research methods, including experiments, theoretical models, and computer simulations. Here are some highlights:

1.     Macromolecular phase separation: Pappu and his team studied the forces that cause molecules to separate into different phases by using a mix of theoretical analysis, computer simulations, and lab experiments. Their work provides a way to compare the forces driving this separation.

2.     NMR spectroscopy on Candida albicans: Fawzi’s team used a technique called NMR spectroscopy to study a protein called Efg1 in the pathogenic yeast C. albicans. They found that temporary helical structures in the protein help it to self-associate and form biomolecular condensates.

3.     Role of lipid droplets and protein condensates: Stachowiak, Parekh, and colleagues report that the surfaces of lipid droplets can help nucleate or form protein condensates, suggesting that these droplets play a role in organizing these cellular structures.

4.     Role of water in phase separation: Havenith’s team used terahertz spectroscopy to measure how water affects phase separation. They found that small energy changes can determine whether phase separation happens.

5.     Viscosity and surface tension of condensates: Shi, Stone, and colleagues developed a new model to measure condensates' viscosity and surface tension by using micropipette aspiration, making it easier to study these properties in the lab.

6.     Multiphasic condensation: Collepardo-Guevara and Reinhardt’s team explored how certain amino acids, like arginine and aromatic residues, drive the formation of complex, multi-layered condensates.

7.     Effect of ATP on DEAD-box helicase: Coupe and Fakhri studied how ATP affects a DEAD-box helicase protein, which helps regulate protein-RNA condensates. They found that ATP changes how the protein interacts with RNA.

8.     Oligonucleotide dynamics: Ameta’s team used fluorescence correlation spectroscopy to study how small pieces of DNA or RNA move within phase-separated droplets, showing how length and charge affect their dynamics.

9.     Nucleolar coarsening: Zidovska’s group investigated how nucleoli (small structures within the nucleus) change and move throughout the cell cycle. They found that changes in chromatin (DNA-protein complex) drive these movements.

10.  Nucleosome core particles: Nordenskiöld’s team studied how ions influence the phase separation of nucleosome core particles, which are fundamental units of chromatin.

11.  HP1α condensates and nuclear stability: Elbaum-Garfinkle’s team linked the properties of HP1α-DNA condensates to the mechanical stability of the nucleus.

12.  Nucleoid size regulation in bacteria: Chang et al. found that polysomes (clusters of ribosomes) and other cytosolic proteins help determine the size of the nucleoid, a membrane-less organelle in bacteria that contains DNA.

13.  p62 condensates and polyQ aggregates: Brangwynne’s team showed that p62 condensates help coarsen polyQ aggregates, affecting the dynamics of protein condensation.

14.  Ubiquitin-binding shuttle proteins: Castañeda’s team studied how different ubiquitin-binding proteins transition into different phases, revealing how specific protein regions influence these transitions.

In addition, two review articles discuss the challenges of studying phase separation involving membranes and condensates and the impact of nucleic acid condensation on the immune system and autoimmune disorders.

Overall, these studies highlight biomolecular condensates' complex and dynamic nature and their importance in organizing and regulating cellular functions.