This CAREER-development plan aims to integrate multidimensional studies at nano-, micro-, and macroscales for a systems based approach to complex biomedical problems linking molecular cell biology and chemistry to physiological (dys)function. Integration of multidimensional studies in tissue optics, mechanobiology and optical clearing will be achieved by interfacing nonlinear optical microscopy (NLOM) with electron microscopy, genomic profiling, biomechanical stress-strain and clinical, in vivo measurements. NLOM is a non-destructive, laser scanning microscopy technique, which can image (sub-) cellular processes in a thick, living tissue specimen over the course of a biological event without fixing, staining or sectioning. Specific imaging of tissue constituents by NLOM will be accomplished via nonlinear optical spectroscopy (e.g., second-harmonic generation and two-photon excited fluorescence). NLOM will be used to monitor tissue structure, organization, composition with (sub-) cellular resolution and changes due to altered mechanical and chemical environments and growth and remodeling.
