Dear Colleagues,

Cells achieve remarkable spatiotemporal control of information flow and metabolism not only through membrane-bound organelles, but also via condensates formed by phase separation, inter-organelle contact sites, and localized biochemical microenvironments that create metabolic niches. This research topic, “Cellular Compartmentalization Beyond Membranes: Condensates, Contacts, and Metabolic Niches,” aims to integrate perspectives across biophysics, cell biology, metabolism, systems biology, and disease to illuminate how these membrane-less and interface-based structures organize cellular function.

Contributions are invited that probe the formation, composition, dynamics, and regulatory logic of biomolecular condensates (e.g., nucleoli, transcriptional hubs, stress granules, lipid droplets, P-bodies) along with the architecture and signaling of membrane contact sites (e.g., ER-mitochondria, ER-plasma membrane, lysosome-organelle, lipid droplet contacts). Equally welcomed are studies on enzyme assemblies, bacterial microcompartments, substrate channeling, and nano-scale physicochemical gradients that define metabolic niches and tune flux. Submissions may span model organisms and cell types, and include original research, reviews, perspectives, methods, and computational modeling.

Key themes include: biophysical principles (phase separation, viscoelasticity, client selection), modulation by RNA, lipids, post-translational modifications, ions and pH, cross-talk between condensates and contact sites, coupling to cytoskeletal and mechanotransductive cues, along with the impact on signaling, gene regulation, organelle homeostasis, and metabolic reprogramming. Particularly encouraged are works leveraging cutting-edge approaches, such as live-cell and super-resolution imaging, cryo-ET, reconstitution, proximity labeling, quantitative proteomics and metabolomics, single-molecule biophysics, microfluidics, as well as integrative computational frameworks, to resolve mechanisms and function at high spatiotemporal resolution.

By bringing together these complementary lines of inquiry, this issue seeks to clarify how cells build and remodel non-membranous compartments and interfaces to achieve robustness, adaptability, and efficiency, and how their dysregulation contributes to cancer, neurodegeneration, infection, and metabolic disease. Ultimately, this issue aims to catalyze conceptual synthesis and methodological innovation that will inform therapeutic strategies and synthetic biology efforts to engineer condensates, contacts, and metabolic niches.

Prof. Dr. Ralf Weiskirchen
Guest Editor