CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells

Cholesterol is an essential component of cellular membranes regulating the structural integrity and fluidity of biological bilayers and cellular processes such as signal transduction and membrane trafficking. However, tools to investigate the role and dynamics of cholesterol in live cells are still scarce and often show limited applicability. To address this, we previously developed a class of imidazolium-based cholesterol analogs, CHIMs. Here we confirm that CHIM membrane integration characteristics largely mimic those of cholesterol. Computational studies in simulated phospholipid bilayers and biophysical analyses of model membranes reveal that in biologically relevant systems CHIMs behave similarly to natural cholesterol. Importantly, the analogs can functionally replace cholesterol in membranes, can be readily labeled by click chemistry and follow trafficking pathways of cholesterol in live cells. Thus, CHIMs represent chemically versatile cholesterol analogs that can serve as a flexible toolbox to study cholesterol behavior and function in live cells and organisms. Matos et al characterise previously developed cholesterol analogues, named CHIMs, which can be fluorescently labelled by click-chemistry. They find that CHIMs segregate similarly to cholesterol in lipid bilayers, allow the visualisation of cholesterol dynamics in cells, and can functionally replace cholesterol in C.elegans.

Automated summary

The study characterizes previously developed cholesterol analogues, named CHIMs, which can replace cholesterol functionally in cell membranes, visualize cholesterol dynamics in cells, and follow cholesterol trafficking pathways in live organisms.