Cationic cell-penetrating peptides (+CPPs) are pervasive killer peptides produced by all animals and found in innate immune systems, venoms and neurodegenerative diseases. Despite their ubiquity, the ...

Focused ion beam (FIB)-milling has been adapted to thin frozen cells for visualization of macromolecular structures in situ with cryogenic electron microscopy. However, only a few large and abundant c...

Nucleosome spacing influences higher-order chromatin fiber organization in vitro but how this relates to cellular chromosome structure remains contentious. To address this, we developed Ligation Analy...

Saleem et al. introduce multi-site DMS-MaP (msDMS-MaP), a chemical probing strategy that permits simultaneous mapping of RNA secondary structures and typically concealed tertiary structures and protei...

This method helps researchers better understand how RNAs work in normal cellular processes and how things go wrong in disease.

Abstract. The liquid–liquid phase-separated environment of the eukaryotic nucleolus is proposed to benefit ribosome assembly by chaperoning rRNA folding an

The solubility product is a rigorous description of the phase boundary for salt precipitation and has previously been shown to qualitatively describe the condensation of biomolecules. Here we present a derivation of the solubility product showing that the solubility product is also a robust description of biomolecule phase boundaries if care is taken to account for soluble oligomers and variable composition within the dense phase. Our calculation describes equilibrium between unbound monomers, the dense phase, and an ensemble of oligomer complexes with significant finite-size contributions to their free energy. The biomolecule phase boundary very nearly resembles the power law predicted by the solubility product when plotted as a function of the monomer concentrations. However, this simple form is concealed by the presence of oligomers in the dilute phase. Accounting for the oligomer ensemble introduces complexities to the power law phase boundary including re-entrant behavior and large shifts for stoichiometrically matched molecules. We show that allowing variable stoichiometry in the dense phase expands the two phase region, which appears as curvature of the phase boundary on a double-logarithmic plot. Furthermore, this curvature can be used to predict variations in the dense phase composition at different points along the phase boundary. Finally, we show how the solubility product power law can be identified in experiments by using dilute phase dissociation constants to account for the oligomer ensemble.

Physics of droplet regulation in biological cells, Zwicker, David, Paulin, Oliver W, ter Burg, Cathelijne

Mutant NPM1 and various leukemia oncofusions form biophysically indistingishable nuclear condensates, termed C-bodies, which orchestrate leukemogenic gene expression. These findings consolidate diverse genetic lesions into a shared pathogenic mechanism in AML.

A hidden structure inside the cell is rewriting how scientists understand leukemia. Beneath the microscope, what looked like disorder turned out to follow...

Biomolecular condensates are made of multiple components but current techniques cannot capture their complex composition quantitatively. Now it has been shown that the dense-phase binodal point defini...

Intrinsically disordered regions (IDRs) in proteins play essential roles in cellular function. A growing body of work has shown that IDRs often interact with partners in a manner that does not depend ...

Ribosome abundance is balanced by production and degradation. Bianco et al. discover that the hibernation factor Stm1 has a dual role in ribosome homeostasis. Stm1 promotes ribosome biogenesis during ...

Protein conformational entropy plays a vital role in functions like binding and catalysis. This Perspective discusses three ways macromolecules use conformational entropy: prepaying entropic costs, re...

The level of cellular organization bridging the mesoscale and whole-cell scale is coming into focus as a new frontier in cell biology. Great progress has been made in unraveling the complex physical a...

Tiny specks called biomolecular condensates are leading to a new understanding of the cell

Biomolecular condensates modulate various ion-dependent cellular processes and can regulate subcellular ion distributions by selective uptake of ions. However, the molecular grammar governing condensa...

The formation of biomolecular condensates is involved in compartmentalisation, regulation, and signalling across most living organisms. Condensation can be driven by phase separation of proteins, and ...

Using a deep neural network and statistical analyses of atomic force microscopy images of individual RNA molecules enables the mapping of RNA conformational space in solution.