Biophysical properties of Lipid Droplets and their implications in Gaucher disease and Parkinson’s disease.

Lipid droplets (LD) are ubiquitous dynamic organelles composed of a neutral lipid core, mainly containing cholesteryl esters (CE) and triacylglycerides (TAG), surrounded by a phospholipid monolayer decorated with different proteins. Dysregulated LD homeostasis have been implicated in many diseases, including in common neurodegenerative diseases, as Parkinson’s disease, cancer and obesity, through yet unknown pathological mechanism. Moreover, our preliminary data have reported accumulation of LD in Gaucher disease cell models with altered biophysical properties. Recent evidence suggests that altered LD neutral core composition, cause changes in LD biophysical properties that drive LD proteome remodeling. Variations in phase properties and organization of LD might also regulate LD interactions with other organelles and thus their ability to reprogram lipid and energy metabolism to meet cellular demands. Thus, LD biophysical changes might reveal one of the mechanisms underlying their biological and pathological roles. Recently, we have shown that Laurdan Generalized Polarization (GP) is a suitable tool to address LD biophysical properties and their change in response to nutrient load and starvation, and pathological conditions, as well as its ability to reflect the TAG/CE composition. Based on this data, I aim to perform a comprehensive study describing relation between LD composition and biophysical properties and consequently use this knowledge to uncover the role of LD in Gaucher diseases (GD) and GD related Parkinson’s disease (PD). The Laurdan GP approach should open the possibility to capture the diverse composition, function, and intra- and inter-cell distribution of LD with high temporal resolution, highlighting its potential widespread use in LD cell biology studies. Together with the study, I will provide a robust methodology protocol and software for data analysis, providing a tool for other researchers aiming to understand the LD pathophysiological role.