Molecular Microscopy of Oil Body and Lipid Droplet Chemistry In Situ with Physiologically-Relevant Readouts

Spatial heterogeneity at the molecular scale is a ubiquitous feature of all biological tissues, which is fundamentally linked to their native functions and to pathology. Probing the local chemistry of complex biological tissues requires the development and application of imaging tools that can identify the intrinsic molecular features in a sample without sacrificing high spatial resolution. In this talk, I will describe our efforts to tackle this challenge for measuring lipid inclusion chemistry and morphology in situ. We have developed nonlinear label-free microscopy and associated analytical tools to determine the biochemistry of lipid droplets and oil bodies with high spatial resolution in a variety of samples. Importantly, our method yields physiologically-relevant quantities (chain length and saturation) as opposed to physical chemical ratios. I will show how we have used this ability to map how lipid droplet chemical composition in brown and white adipose tissue adapts to high fat dietary intervention. Going forward, we want to expand the disease pathologies studied and I will present early results on our work on lipid droplets in neurological diseases