Aims & Scope

Cellular signaling is first initiated at the plasma membrane, and orchestrated by cell surface receptors, ion channels, adhesion molecule complexes, and lipids assemble into dynamic, nanoscale signaling platforms. These membrane architectures integrate biochemical and mechanical cues to regulate signal transduction, trafficking, and gene expression programs that underlie development, metabolic control, and homeostasis. At the molecular level, interactions of specific ligand-receptor pairs, membrane lipids, scaffolding proteins, cytoskeletal elements, and post-translational modifications confer signaling specificity, temporal precision, and pathway bias. Disruption of cellular signaling—through genetic variation, inflammation, metabolic stress, or injury—rewires signaling networks and contributes to metabolic, neurological, endocrine, and stress-related disease. Rapid advances in super-resolution imaging, quantitative biophysics, and single-cell and spatial omics now enable direct interrogation of these mechanisms in physiological and pathological contexts. The Collection in this journal will focus on mechanistic studies that define how membrane signaling architectures encode cellular decisions and how these pathways can be therapeutically modulated

Goals / Objectives:

This Collection aims to elucidate fundamental molecular and cellular principles governing cell signaling organization and function. Specifically, we seek to (i) define how extracellular ligands interactions with receptors, lipids, scaffolds, and cell adhesion molecules to convey signals intracellularly to cytoskeletal networks and trafficking machinery to regulate gene expression and protein translation; (ii) identify context-dependent signaling states and failure modes that drive disease-relevant phenotypes; and (iii) uncover mechanistically grounded intervention points. Emphasis will be placed on studies linking molecular signaling events to cellular outcomes, with attention to variability arising from developmental stage, sex, and metabolic state. A complementary goal is to highlight translational insights that emerge from mechanistic discovery, including identification of druggable targets and strategies to bias, restore, or reprogram membrane signaling. Together, these efforts aim to establish conceptual frameworks that bridge molecular mechanism with therapeutic opportunity.

Scope (sub-areas to be included):

• Molecular organization and dynamics of membrane nanodomains (e.g., lipid rafts, caveolae, tetraspanin networks) and their roles in ligand-receptor signaling, such as but not limited to: GPCR, RTK, and ion-channel signaling.
• Lipid–protein interactions, scaffolding complexes, and post-translational modifications that regulate signaling specificity, bias, and duration.
• Integrins, adhesion complexes, and membrane–cytoskeleton coupling as regulators of mechanotransduction and signal integration.
• Coordination of membrane signaling with intracellular trafficking, secretion, and cytoskeletal remodeling.
• Developmental and adaptive rewiring of membrane signaling pathways and their contributions to endocrine and metabolic disease.
• Disease-associated perturbations of membrane signaling in obesity, diabetes, reproductive disorders, inflammation, stress-related conditions, and aging.
• Therapeutic strategies informed by mechanism, including biased agonists, allosteric modulators, channel and adhesion regulators, lipid remodeling approaches, and targeted delivery platforms.
• Experimental systems spanning advanced imaging, single-cell and spatial omics, quantitative modeling, human tissues, stem-cell–derived models, organoids, and in vivo