Tissue stiffness mapping by light sheet elastography

Tissue stiffness plays a crucial role in regulating morphogenesis. The ability to measure and monitor the dynamic progression of tissue stiffness is important for generating and testing mechanistic hypotheses. Methods to measure tissue properties in vivo have been emerging but present challenges with spatial and temporal resolution especially in 3D, by their reliance on highly specialized equipment, and/or due to their invasive nature. Here, we introduce light sheet elastography, a noninvasive method that couples low-frequency shear waves with light sheet fluorescence microscopy by adapting commercially available instruments. With this method, we achieved in toto stiffness mapping of organ-stage mouse and zebrafish embryos at cellular resolution. Versatility of the method enabled time-lapse stiffness mapping during tissue remodeling and of the beating embryonic heart. This method expands the spectrum of tools available to biologists and presents opportunities for uncovering the mechanical basis of morphogenesis.