Interactions between lipid membranes and peripheral membrane proteins are essential to many physiological processes. Assays that use liposomes as artificial membranes are widely used because they allow for the creation of lipid mixtures that closely approximate native membrane environments. However, many of these assays require large quantities of lipids and purified proteins, and it is often difficult to scale up lipid production protocols. In addition, once produced, lipids are stable in biological buffers for only a few days. Now, Gavin and colleagues have devised a liposome microarray–based assay (LiMA) that uses liposomes assembled from lipid mixtures that have been soaked into a thin agarose layer (TAL). The authors apply spots of lipid mixtures composed of signaling lipids, such as glycerophospholipids and sterols, the carrier lipid POPC and a fluorescently labeled lipid, such as PE-Atto 647, on the TAL. The lipid-spotted TAL could be stored under argon for at least 2 months. For the binding assays, the TAL was coupled to a microfluidic chamber, and a GFP-tagged lipid-binding protein was introduced. The authors' final device contained four different chambers, thus permitting the examination of four different signaling proteins interacting with 30 different lipid membranes. After incubation, imaging was performed on an automated fluorescence microscopy platform, and the number of GFP-tagged proteins bound per unit of membrane surface area was calculated. LiMA can be used to detect cooperative binding events and discrete changes in binding affinities brought about, for example, by protein mutation. It has the potential to be scaled to proteomic or lipidomic analyses and can make use of the readily available cell lines producing GFP fusions. (Nat. Methods doi:10.1038/nmeth.2734, 24 November 2013)