Dear Editor,

The appearance of phosphatidylserine (PS) on the cell surface is one of the hallmarks of the early/intermediate stages of cell apoptosis, and is believed to occur prior to DNA fragmentation, morphological changes, and plasma membrane permeabilization.1 The clearest assessment of cell apoptosis is gained from microscopy or flow cytometry analyses that examine large cell populations and identify and quantify subpopulations. A common method of detecting PS on a cell surface is to use the PS-binding protein annexin V.2,3 This 35 kDa protein is typically labeled with a fluorescent dye, often fluorescein because it can be conveniently excited by an argon laser. Although annexin V is a useful reagent, it is an expensive protein, and there are some technical drawbacks. One concern is that up to 2.5 mM of extracellular Ca2+ may be needed for complete membrane binding. This can lead to false-positive results because most animal cells have a Ca2+-dependent scramblase that can move PS to the cell surface. In addition, annexin V is known to associate with membrane surfaces that contain the by-products of lipid peroxidation.4 Furthermore, complete annexin binding requires incubations times of up to 1 h, which is problematic for kinetic assays.5 In summary, dye-labeled annexin V is used extensively as a PS-sensing reagent, but there is a need for a low-molecular-weight mimic that can sense PS-rich membranes rapidly and independently of Ca2+ levels.

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