Biomembranes exhibit specific lipid organization, such as transbilayer asymmetry and domain structures. However, detailed organization of lipids is not well understood mainly because of the lack of specific and reliable tools to image lipids. One strategy to visualize endogenous lipids is to label them. Several lipid-specific antibodies are reported. However, very few proteins have been reported that bind specific lipids.

One of the characteristic features of lipids is its diversity among animal kingdoms. Various organisms have developed protein and peptide toxins that strongly bind specific lipids that the producing cells do not contain. Non-toxic derivatives of these toxins recently become useful and powerful tools to image lipids. In this Colloquium, I will summarize our attempt to image lipids, especially lipid rafts (i.e. sphingolipid-cholesterol complex), using lipid-binding toxins in combination with various advanced microscope techniques. Such approaches provide insights into the organization and the dynamics of lipids in various pathophysiological conditions.