Single-Molecule Biosensors: Revealing Molecular Heterogeneity and Dynamics in Chemical Biology

Biological samples contain rich mixtures of molecular states whose signals arise from secondary structures, conformational changes, post-translational modifications, and biomolecular association and dissociation. In bulk measurements, these contributions are averaged together, making it difficult to quantify distinct populations or interpret mechanisms at molecular resolution. The emergence of single-molecule techniques has transformed how biomolecules are measured by allowing individual molecules, rather than ensemble averages, to be observed, manipulated, and quantified. From fluorescence-based sensing to mechanical manipulation, single-molecule approaches reveal hidden distributions, transient intermediates, rare events, and microstates that are often invisible to conventional methods. This information is essential for understanding how biomolecules fold, bind, catalyze, regulate, and perform their functions in vitro and in vivo.The goal of this Research Topic is to highlight how single molecule approaches are transforming chemical biology by revealing molecular heterogeneity, transient states, rare events, and dynamic pathways that are hidden in ensemble measurements. We welcome studies that use single molecule fluorescence, force spectroscopy, nanopores, high-resolution imaging, and computational approaches to connect molecular distributions with biological function and outputs. Emphasis will be placed on work that uses single molecule measurements not only as a technical platform, but as a discovery tool for uncovering mechanisms of folding, binding, catalysis, regulation, transport, sensing, and molecular recognition. By bringing together experimental and theoretical perspectives, this collection aims to define how single molecule measurements can bridge molecular detail, biological complexity, and quantitative interpretation.· Single molecule studies for discovery· Beyond the ensemble: single molecule measurements· Advances in single molecule measurement for medical biophysics· Mechanical manipulation: manipulating conformations and measuring forces· Nanopore resistive pulse sensors· Computational approaches bridging the gap between theory and experiment.Please note: Review articles can be submitted by invitation only. Topic editors: Joseph Robertson, Rodrigo Maillard Source: https://www.frontiersin.org/research-topics/83543/single-molecule-biosensors-revealing-molecular-heterogeneity-and-dynamics-in-chemical-biology