Deformation microscopy for dynamic intracellular and intranuclear mapping of mechanics with high spatiotemporal resolution

Structural heterogeneity is a hallmark of living cells and nuclei that drives local mechanical properties and dynamic cellular responses, including adhesion, gene expression, and differentiation. However, robust quantification of intracellular or intranuclear mechanics are lacking from conventional methods. Here, we describe new development of deformation microscopy that 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 nuclei. Using deformation microscopy, we found that tensile loading modes dominated intranuclear architectural dynamics in cardiomyocytes in vitro or myocytes in vivo, which was compromised by disruption of LINC complex molecule nesprin-3 or Lamin A/C, respectively. We also found that cells cultured on stiff substrates or in hyperosmotic conditions displayed abnormal strain burden and asymmetries compared to controls at interchromatin regions where active translation was expected. Deformation microscopy represents a foundational approach toward intracellular elastography, with potential utility to provide new mechanistic and quantitative insights in diverse mechanobiological applications.