Isolated plasma membranes separate into two coexisting liquid phases with distinct lipid and protein compositions but live cell plasma membranes do not macroscopically phase separate, leading to questions of whether and how the membrane phase transition contributes to functional heterogeneity in cells. Using quantitative super resolution microscopy we show that B cell receptor signaling platforms are nanoscale domains that quantitatively enrich membrane probes based on probe phase partitioning in isolated plasma membrane vesicles. Phase partitioning in vesicles also predicts relative probe mobility and retention at receptor clusters. The convergence between measurements in live cells and isolated membranes establishes a clear role for the membrane phase transition as an organizing principle in cells. We propose that physical properties fundamental to the membrane phase transition give rise to a plasma membrane that is a highly responsive medium, capable of compartmentalizing cellular processes in response to diverse stimuli.
Membrane phase separation drives organization at B cell receptor clusters