Deformation Microscopy for Dynamic Intracellular and Intranuclear Mapping of Mechanics with High Spatiotemporal Resolution

Structural heterogeneity is a hallmark of living cells that drives local mechanical properties and dynamic cellular responses. However, the robust quantification of intracellular mechanics is lacking from conventional methods. Here, we describe the development of deformation microscopy, which leverages conventional imaging and an automated hyperelastic warping algorithm to investigate strain history, deformation dynamics, and changes in structural heterogeneity within the interior of cells and cell nuclei. Using deformation microscopy, we found that partial or complete disruption of LINC complexes in cardiomyocytes in vitro and lamin A/C deficiency in myocytes in vivo abrogate dominant tensile loading in the nuclear interior. We also found that cells cultured on stiff substrates or in hyperosmotic conditions displayed abnormal strain burden and asymmetries at interchromatin regions, which are associated with active transcription. Deformation microscopy represents a foundational approach toward intracellular elastography, with the potential utility to provide mechanistic and quantitative insights in diverse mechanobiological applications. [Display omitted] •Deformation microscopy is developed by combining imaging and advanced mechanics•Modulation of nuclear LINC proteins or lamin A/C reveals altered intranuclear strain•Abnormal mechanical environments cause abnormal strain in high-density chromatin•Hyperosmotic conditions lead to nuclear strain asymmetry mediated by the cytoskeleton Ghosh et al. show that deformation microscopy, a technique based on image analysis and mechanics, reveals deformation dynamics and structural heterogeneity changes for several applications and at multiple scales, including tissues, cells, and nuclei. They reveal how the disruption of nuclear proteins and pathological conditions abrogate mechanical strain in the nuclear interior.