Cell Physiology

Cell physiology examines how living cells maintain internal order, communicate with each other and their environment, and convert substrates into energy and molecular building blocks. At its core are processes such as selective membrane transport, signal transduction via receptors and kinases, intracellular ionic homeostasis, and metabolic pathway regulation. Cells rely on a dynamic lipid bilayer studded with specialised channels, pumps and receptors to control the entry and exit of ions and nutrients, while cytoskeletal elements determine shape, polarity and motility. Within the cytoplasm, membrane-bound organelles compartmentalise reactions—from protein synthesis on ribosomes and post-translational modification in the endoplasmic reticulum and Golgi apparatus, to ATP generation in mitochondria and macromolecule turnover in lysosomes and peroxisomes. Gene expression is controlled by nuclear–cytoplasmic interactions, with chromatin remodelling and transcription factor cascades responding to extracellular cues. Together, these systems allow cells to sense mechanical and chemical stimuli, reprogramme metabolism for growth or repair, and coordinate complex behaviours such as proliferation, differentiation and programmed death.

Research from Nature Portfolio

New insights into endothelial junction physiology have revealed that engagement of the CD31 receptor on vascular cells triggers a rapid, Src-dependent shift to glycolysis. This metabolic reprogramming sustains junction re-annealing after acute inflammatory disruption, restoring barrier integrity through Akt-mediated transcriptional events and β-catenin nuclear translocation.

Glutamate, long recognised for its action on neuronal NMDARs, has now been shown to function as a positive allosteric modulator of ASIC1a channels. By enhancing proton affinity and channel open probability, glutamate exacerbates acidosis-induced neurotoxicity in ischaemic stroke models. Structure-guided discovery of a small molecule that selectively blocks the glutamate-binding cavity on ASIC1a spares NMDARs, reduces infarct size and improves functional recovery.

Cryo-EM structures of the FMRFamide-gated DEG/ENaC channel (FaNaC1) have delineated the ligand-binding site and captured conformational changes upon activation. These findings illuminate the gating mechanics shared across ENaC-related families—including proton-gated ASICs—providing a molecular template for dissecting pH-sensing and for rational design of selective modulators.

Cell Physiology publication trend

The graph below shows the total number of articles in cell physiology across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolic reprogramming: The rapid shift of cellular energy pathways, especially towards glycolysis, to support specific functions such as junction repair.

Acid-sensing ion channel (ASIC): A proton-gated cation channel in the DEG/ENaC family that responds to extracellular acidification with Na⁺ influx.

Allosteric modulation: Regulation of channel or enzyme activity by ligand binding at a site distinct from the active or pore region.

Cryo-electron microscopy (cryo-EM): A technique for determining near-atomic structures of proteins or complexes in a frozen hydrated state.

Ball-and-chain gating: A mechanism whereby a peptide segment (ball) transiently occludes the ion-conducting pore from the intracellular side.

Neural progenitor cell (NPC): A precursor cell in the central nervous system capable of migration, proliferation and differentiation into neurons and glia.

References

1. Cell Structure and Biochemical Reactions.
2. Structural basis for excitatory neuropeptide signaling. Nature Structural & Molecular Biology (2024).
3. CryoEM structures of the human CLC-2 voltage-gated chloride channel reveal a ball-and-chain gating mechanism. eLife (2024).
4. Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming. Nature Communications (2020).
5. Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury. Nature (2024).
6. Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke. Research (2023).