Analysis of membrane fluidity disturbances by mutant huntingtin in different membranal compartments using phasor analysis of local ICS and spectral phasor analysis

Huntington's Disease (HD), caused by the expression of extended polyQ repeats in the protein huntingtin, is known to disturb cholesterol metabolism. The misfolded proteins alter biosynthesis and intracellular levels of cholesterol, leading to membranes deterioration. In this work, we aim to describe the effect of said disturbances in various membrane compartments caused by different polyQ expansions from the membrane fluidity point of view, an approach never applied before. To this end, we use the environment-sensitive fluorescent probe LAURDAN to study the membrane fluidity at different compartments of SHSY5Y cells modified to express the non-pathogenic (18QmCherry) and pathogenic (53QmCherry, 77QmCherry) protein.