Mechanochemical regulation of nucleic-acid structure and function

Nucleic acids adopt diverse and dynamic structures that play central roles in genome organization, gene regulation, and cellular function. Beyond sequence and chemical composition, the folding, stability, and interactions of nucleic-acids are strongly influenced by mechanical forces and physicochemical environments within cells. Forces generated by molecular motors, chromatin remodeling complexes, transcriptional machinery, and intracellular fluid dynamics continuously act on nucleic acids, modulating their structural transitions and regulatory functions. Recent advances in single-molecule, nanoscale, and high-throughput technologies now enable direct interrogation of nucleic acid mechanics, conformational dynamics, and assembly pathways with unprecedented precision. This Research Topic highlights emerging genomic assay technologies, experimental platforms, and analytical approaches that quantify force-dependent nucleic acid behavior and link mechanical perturbations to functional genomic outcomes.The primary goal of this Research Topic is to establish a rigorous and quantitative framework and standardized assays for understanding how mechanical forces regulate nucleic acid structure, dynamics, and biological function across molecular and supramolecular scales. We encourage contributions that extend beyond bespoke experiments toward scalable and automated assay platforms including multiplexed force spectroscopy, microfluidic systems, and integrated technologies that enable systematic mapping of force-dependent structure-function relationships. Although single-molecule studies have revealed key principles of nucleic-acid mechanics, major gaps remain in linking force-driven conformational transitions to biological activity. In particular, the influence of mechanical constraints on folding pathways, stability landscapes, ligand recognition, and interactions with proteins and higher-order assemblies remains incompletely understood.This Topic seeks studies that combine high-resolution experimental approaches with computational and theoretical modeling to develop and validate assays that reveal the physical basis of nucleic-acid mechano-functional chemistry. By integrating interdisciplinary perspectives, we aim to illuminate how mechanical forces shape genome regulation, biomolecular assembly, and disease-associated processes, connecting molecular measurements to genotype–phenotype and genome-function questions, while enabling new technologies for probing and manipulating nucleic acid function.This Research Topic welcomes original research articles, reviews, and methodological papers addressing mechanochemical regulation of DNA and RNA structures and functions. Topics of interest include, but are not limited to:- Force-regulated nucleic acid folding and unfolding- Single-molecule studies using AFM, optical/magnetic tweezers, single-molecule imaging/super-resolution microscopy, and related techniques- DNA nanotechnology-based platforms (e.g., DNA origami, nanoswitch calipers) for applying, calibrating, and measuring force on nucleic acids- Mechanochemical modulation of nucleic acid-protein and nucleic acid-ligand interactions- Mechanical control of nucleic acid stability and assembly pathways- Regulation of biochemical processes under force (e.g., replication, repair, transcription, and genome maintenance)- Nucleic acid mechanics in biomolecular condensates and phase-separated systems- Computational and theoretical modeling of force-dependent nucleic acid behavior- Assays for nucleic acid-protein assemblies relevant to genome function (e.g., chromatin, remodelers, polymerases, topoisomerases) under controlled mechanical constraints- Benchmarking, calibration, and standards for force measurements, comparability, and reproducibility- Multiplexed and/or high-throughput force spectroscopy platforms and assay automation- Computational pipelines for data processing, kinetic/energy landscape inference, storage, and sharing of single-molecule datasets Topic editors: Pravin Pokhrel, Deepak Karna, Prakash Shrestha, Sagun Jonchhe Source: https://www.frontiersin.org/research-topics/79663/mechanochemical-regulation-of-nucleic-acid-structure-and-function