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Eukaryotic cells sense and decode chemical and mechanical signals via plasma membrane receptors such as integrins. Evidence, including our own1, shows the plasma membrane encodes, amplifies, and feeds back on these extracellular cues. How can a compositionally heterogeneous fluid bilayer process information? We find that upon integrin activation, cells generate localized mesoscale liquid-ordered membrane domains (“active emulsions”2) downstream of RhoA signaling and mechanotransduction1. These domains encode substrate chemistry and mechanics, regulating integrin function, cell spreading, and migration. Such organization arises from engagement with myosin motors, a dynamic cortical actin meshwork, and actively maintained bilayer asymmetry, creating an ATP-fueled, mechano-responsive medium integrating peripheral cues. 1. PMID: 31104842; 2. PMID: 35867835
