Exploring Basement Membrane Dynamics through Cross-Scale Imaging, Manipulation, and Molecular Mapping.

The basement membrane (BM), a specialized extracellular matrix (ECM), provides structural support for epithelial, endothelial, and other parenchymal cells. Once considered a static scaffold, the BM is now recognized as a dynamic and complex nanostructure composed of a diversity of molecules that actively regulate cell behavior and tissue organization. Its molecular composition, assembly, and remodeling are precisely controlled in a tissue- and stage-specific manner, contributing to the regulation of local and global mechanical properties and biochemical signaling. Understanding BM structure and function requires integrated approaches across biological scales-from nanoscale molecular interactions to tissue-level architecture. In this review, we highlight advances in three methodological areas: (1) imaging techniques that reveal BM nanostructure and dynamics, (2) manipulation strategies that uncover causal roles of BM components, and (3) omics-based approaches that map BM composition and cellular sources. Integrating these strategies enables the bridging of molecular events and organ-level functions, offering new insights into how the BM is involved in development, homeostasis, and disease progression. The aim of this review is to provide researchers with a comprehensive perspective on evolving tools for dissecting BM structure, dynamics, and function.