Photoluminescence switches with ultralarge stokes shift for cellular membrane lipid order imaging

Lipid order in cellular membranes plays a critical role in cellular functions and is implicated in various pathological conditions. Reliable detection tools are essential for elucidating the biological mechanisms of diseases initiated by lipid order alterations and for monitoring disease progression. Herein, we report a solvatochromic probe with an ultralarge Stokes shift of approximately 200 nm based on indanonealkene luminescent platform, for distinguishing plasma membrane lipid order. Theoretical calculations corroborated the probe's twisted intramolecular charge transfer properties, and cellular experiments validated its cell membrane targeting and lipid order discrimination capabilities, further confirmed in giant unilamellar vesicles models. Furthermore, the probe TPA-CA-3 allows the detection of dynamic lipid order variations in live cells under mechanical force, cholesterol depletion, and cholesterol enrichment. We anticipate that this large Stokes shift fluorescence probe will serve as a valuable tool for tracking and quantifying lipid order across diverse biological processes.