The TissueTractor: A Device for Applying Large Strains to Tissues and Cells for Simultaneous High‐Resolution Live Cell Microscopy

Mechanical strain substantially influences tissue shape and function in various contexts from embryonic development to disease progression. Disruptions in these processes can result in congenital abnormalities and short‐circuit mechanotransduction pathways. Manipulating strain in live tissues is crucial for understanding its impact on cellular and subcellular activities, unraveling the interplay between mechanics and cells. Existing tools, such as optogenetic modulation of strain, are limited to small strains over limited distances and durations. Here, a high‐strain stretcher system, the TissueTractor, is introduced to enable simultaneous high‐resolution spatiotemporal imaging of live cells and tissues under strain applications varying from 0% to over 100%. We use the system with organotypic explants from Xenopus laevis embryos, where applied tension reveals cellular strain heterogeneity and remodeling of intracellular keratin filaments. To highlight the device's adaptability, the TissueTractor is also used to study two other mechanically sensitive cell types with distinct physiological roles: human umbilical vein endothelial cells and mouse neonatal cardiomyocytes, revealing cell morphological changes under significant strain. The results underscore the potential of the TissueTractor for investigating mechanical cues that regulate tissue dynamics and morphogenesis.