ECM–Immune Interface and Single‑Cell Biophysics—Mechanisms, Models, and Translational Frontiers across Tissues

In recent years, biophysical investigations of the extracellular matrix (ECM) and the immune system have reshaped understanding of tissue homeostasis and disease. Advances now reveal how matrix composition, mechanics, and topology influence immune cell fate and function, from antigen sensing and trafficking to inflammatory resolution, while immune-derived enzymes, cytokines, and proteases reciprocally remodel the ECM. Concurrently, single-cell and spatial multi-omics, advanced imaging, organoids, and computational modeling are uncovering the cellular heterogeneity and microenvironmental cues that govern these bidirectional interactions across ocular, mucosal, neural, vascular, and tumor tissues. The convergence of ECM biology, immunology, and quantitative biophysics is enabling mechanism-rich, translationally focused discovery.This Research Topic aims to highlight breakthroughs and emerging paradigms at the ECM–immune interface, emphasizing single-cell and spatially resolved biophysics that bridge molecular mechanisms with tissue-level function and pathology. By assembling contributions from matrix biology, immunology, bioengineering, and computational modeling, the collection seeks to clarify how ECM architecture, mechanics, and glycobiology regulate immune surveillance, tolerance, and inflammation, and how these principles can be leveraged for diagnostics and therapy.Manuscripts are welcomed that address, but are not limited to, the following themes:- Biophysical regulation of immune cells by ECM composition, mechanics, and topology (e.g., stiffness, porosity, ligand presentation)- Roles of proteoglycans and glycosaminoglycans (e.g., lumican, biglycan) in innate and adaptive immune signaling, TLR pathways, and antigen handling- Single-cell and spatial multi-omics of ECM–immune niches in health and disease (ocular surface, cornea, retina, mucosa, skin, vasculature, CNS, tumor microenvironments)- Organoids, ex vivo tissues, and microphysiological systems for modeling ECM–immune crosstalk and therapeutic responses- Imaging and biophysical methodologies (super-resolution, traction force microscopy, AFM, live-cell and intravital imaging, PET/optical probes) for quantifying ECM–immune interactions- Computational modeling and AI/ML for integrative analysis of ECM remodeling, cell–matrix mechanics, and immune network dynamics- ECM cues in immune cell differentiation and function, including TH1/Treg balance, macrophage polarization, dendritic cell maturation, and cytotoxic responses- Matrix remodeling in infection, autoimmunity, neuroinflammation, fibrosis, wound healing, and cancer immunity; links to disease progression and resolution- Glycobiology, post-translational modifications, and protease networks shaping receptor trafficking and signaling at the ECM–immune interface- Translational applications: biomarkers, imaging agents, mechanotherapeutics, matrix-targeted or immunomodulatory drugs, and delivery systems- Methodological advances for measuring and perturbing ECM–immune interactions at single-cell resolution, including open-source tools and standardsThe Research Topic invites original research, reviews, perspectives, among other article types. Multidisciplinary studies that integrate experimental and computational approaches, connect single-cell resolution with tissue-scale phenotypes, or establish clinically relevant models are especially encouraged.By promoting cross-disciplinary exchange and highlighting cutting-edge methods, this Research Topic aims to catalyze a mechanistic, quantitative understanding of ECM–immune crosstalk and to accelerate translation into diagnostics and therapies across diverse tissues and diseases. Topic editors: Tanaya Roychowdhury, George Maiti, Grady Nelson Source: https://www.frontiersin.org/research-topics/76284/ecm-immune-interface-and-single-cell-biophysics-mechanisms-models-and-translational-frontiers-across-tissues