Detection of molecular interactions at membrane surfaces through colloid phase transitions

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Abstract
The molecular architecture of—and biochemical processes within—cell membranes play important roles in all living organisms, with many drugs and infectious disease agents targeting membranes. Experimental studies of biochemical reactions on membrane surfaces are challenging, as they require a membrane environment that is fluid (like cell membranes) but nevertheless allows for the efficient detection and characterization of molecular interactions. One approach uses lipid membranes supported on solid substrates such as silica or polymers1,2: although the membrane is trapped near the solid interface, it retains natural fluidity and biological functionality3 and can be implanted with membrane proteins for functional studies4. But the detection of molecular interactions involving membrane-bound species generally requires elaborate techniques, such as surface plasmon resonance 5 or total internal reflection fluorescence microscopy6. Here we demonstrate that colloidal phase transitions of membrane-coated silica beads provide a simple and label-free method for monitoring molecular interactions on lipid membrane surfaces. By adjusting the lipid membrane composition and hence the pair interaction potential between the membrane-supporting silica beads, we poise our system near a phase transition so that small perturbations on the membrane surface induce dramatic changes in the macroscopic organization of the colloid. We expect that this approach, used here to probe with high sensitivity protein binding events at membrane surfaces, can be applied to study a broad range of cell membrane processes.