Volume 22 Issue 8, August 2026

The interface between biomolecular condensates and cellular membranes underlies many biological processes, yet how biomolecules and lipids reciprocally influence one another’s phase behavior remains poorly understood. A study now shows that membrane composition modulates biomolecular condensation on the membrane, pointing to a new regulatory mechanism of condensation in cells.

Understanding protein glycosylation is essential to decode complex cellular networks. A systems-level approach that networks substrate and interacting proteins of O-GlcNAc transferase, the sole enzyme catalyzing O-GlcNAcylation on thousands of proteins, provides insights into the functional relationship of O-GlcNAcylation and coordinated cellular signaling networks.

The function of membrane proteins is dependent on the lipid environment, but whether this is due to high-affinity, ligand-like linkage is unclear. Extensive molecular dynamics simulations and single-molecule photobleaching measurements now show that the dimerization of a chloride transporter is instead controlled by a preferential solvation mechanism.

Structure-based binding affinity prediction has to navigate a trade-off between accuracy and throughput. Now, PBCNet2.0 learns geometry-aware pairwise affinity changes at scale, delivering free energy perturbation-competitive ranking accuracy while offering interpretable interaction insights and emergent sensitivity to binding-pocket mutations.

The gut microbiome converts dietary fiber into metabolites that shape human health, but identifying the right combinations of microorganisms and nutrients has been a challenge. A machine learning framework can now find optimal microbial communities that maximize targeted health benefits in the gut.

Bowl-shaped mechanosensitive PIEZO channels sense membrane tension by flattening curved transmembrane domains, but how these mechanosensory motions couple with and open the channel pore is unclear. Now, multi-scale molecular dynamics simulations provide insight into this mechano-electrical coupling in PIEZO2, uncovering clockwork-like gating motions of the central pore.

Mechanosensitive PIEZO channels sense and open through membrane tension, but their dynamic gating mechanisms at the molecular level remain unclear. A hybrid all-atom and coarse-grained molecular dynamics simulation approach and electrophysiology reveal a clockwork mechanism for PIEZO2 involving two open states.

Static protein structures can capture the association of lipids, but it is unclear whether the association is due to lipids acting as long-lived ligands or the solvation of preferred lipids around the protein. A computational-experimental framework has now shown that for the protein CLC-ec1, it is the change in lipid solvation energies that drives dimerization, with preferred lipids around the protein modulating this driving force.

Biopolymers can couple to membrane lipids and condense to prewet membranes. Here a range of membrane perturbations in reconstituted systems and cells show that the prewetting is sensitive to membrane composition and phase transitions and can drive interorganelle contact.

Sequence biases at individual positions can be used to design more stable protein variants, while correlation between pairs of residues has also been shown to be important for specifying protein structure and function. Here, a Potts model is used to separate the contributions of single-site biases and pair correlations, revealing that protein structure is stabilized by single-site biases rather than pairwise coupling, while pairwise coupling is important for protein function.

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

Pei, Wang, Quan and Geng and colleagues reveal how amino acid composition within intrinsically disordered regions influences the miscibility of biomolecular condensates and their function. Serine and aromatic residues promote condensate miscibility, while charged residues drive immiscibility. Serine phosphorylation acts as a miscibility switch.

Dietary fibers are a primary energy source for gut bacteria and shape the composition and function of the microbiome. Now, an active learning approach integrating explainable machine learning, Bayesian optimization and high-throughput community construction designs microbial communities with desired functions in response to key nutrients.

Protein–ligand binding affinity prediction is important for the development and optimization of molecular probes. PBCNet2.0 predicts relative affinity changes induced by ligand modifications (for example, functional groups and stereochemistry) and shows an emergent capability to predict affinity shifts caused by binding pocket residue mutations.

By analyzing the structures of the Polycomb repressive deubiquitinase complex, which catalyzes the deubiquitination of H2AK119Ub on nucleosomes, Zhang, Zheng, Tong and Deng et al. reveal that ubiquitin acts as a proteinaceous glue to fasten the intersubunit interaction within the complex to allosterically enhance its activity.

A ratiometric fluorescent probe that maps absolute mitochondrial Na⁺ at single-organelle resolution and works independently of membrane potential has now been developed. The probe called MitRatiNa reveals striking heterogeneity in mitochondrial Na⁺, its dynamic coupling to Ca²⁺ influx, and its alteration in metabolic stress and mitochondrial disease.

This study reveals that adhesion G-protein-coupled receptors (GPCRs) promote extracellular vesicle (EV) formation and EVs spread GPCRs into neighboring cells to activate G-protein signaling, providing a novel mechanism for cell–cell communication.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

Membrane-permeable cyclic peptides offer access to difficult intracellular targets but discovery remains challenging. Here the authors show that cell-active cyclic peptides can be identified by screening sufficiently large and diverse libraries of small synthetic peptides.