Conceptual visualization of the Glyco-PAINT method. Sugar molecules tagged with a fluorescent marker (in red) bind reversibly to the mannose receptors anchored on the cell membrane, which allows tracking of their movements and provides information on binding affinity and receptor mobility in living cells.

See Riera et al.

Luminescent and cell-permeable macrocyclic terbium complexes called CoraFluors enable the detection of ligand–target engagement in cells by time-resolved FRET. The image shows a protein target (in purple) lit up by CoraFluors.

See Payne et al.

The human gut bacterium Clostridium scindens produces the secondary bile acids deoxycholic acid and lithocholic acid, which have protective effects in diabetes and other diseases. The image shows C. scindens (in pink) on a human intestinal epithelial cell, demonstrating the close physical relationships between microbiome and host cells.

SeeDevlin et al.

The FIND-IT assay deploys two different CRISPR nucleases in tandem and a chemically stabilized activator to accelerate the detection of RNA for diagnostics. The cover image depicts the processes by which the Cas13a and Csm6 nucleases in tandem recognize the target RNA and activate fluorescent reporters.

See Liu et al.

Collagen undergoes elevated cross-linking during diseased conditions due to increased expression of an enzyme called lysyl oxidase (LOX). This image depicts the areas of active collagen remodeling around the boundaries of a skin tumor section revealed by a peptide-based blue fluorescent probe.

SeeAronoff et al.

A small-molecule activator of Hippo–YAP signaling interacts with Annexin A2 (ANXA2) to enable YAP-mediated epidermal keratinocyte expansion. The cover art is a watercolor image of the epidermal layer of the skin mimicking images observed from histological analysis.

SeeShalhout et al. and Moroishi

Cells undergoing ferroptosis, an oxidative form of cell death, exhibit an accumulation of oxidized lipids at the plasma membrane. The cover image depicts a dying HT-1080 cell with lipids visualized as a glowing green ‘ring of death’ using a lipid reactive oxygen species probe.

See Dixon et al. and Birsoy et al

In response to the invasive mite Varroa destructor, honey bees (Apis mellifera) produce six Varroa-paratization-specific compounds that trigger recognition of a parasitized brood and induce the bees’ hygienic response to defend against the parasite.

See Mondet et al.

The cover illustrates the synthetic protein quality control (ProQC) system, in which a 5’ toehold switch hybridizes with a trigger sequence at the 3’ end of the mRNA to facilitate ribosomal translation of full-length proteins.

See Yang et al.

Single-molecule FRET sensors made by incorporating unnatural amino acids shed light on the mechanism of allosteric activation in mGluR2 metabotropic glutamate receptors, revealing how conformational changes of the ligand-binding domain with loose coupling to the cysteine-rich domain propagate during receptor activation.

See Liauw et al.

Genetic and chemical perturbations in petunia flowers reveal that the cuticle acts as a sink for volatiles during emission to prevent cellular damage. Alteration of the cuticle affects emission of different volatiles depending on their physiochemical properties.

See Liao et al.

In yeast, targeting potentially toxic proteins to the peroxisome (here demonstrated with yellow fluorescent protein) protects the cell from harmful effects. Using this peroxisome-targeting approach with the toxic enzyme norcoclaurine synthase enables increased production of (S)-reticuline and other alkaloids.

See Grewal et al.