Optogenetic strategies for optimizing the performance of biosensors of membrane phospholipids in live cells

Abstract

AbstractHigh-performance biosensors are crucial for unraveling the intricate spatiotemporal regulatory roles and dynamics of membrane lipids. However, there remains a significant challenge in improving the sensitivity and substrate detection capabilities of phospholipid biosensors, particularly for low-content substrates. Here we presented universal optogenetic strategies aimed at enhancing a range of membrane biosensors. These strategies involve the precise localization of biosensors within specific membrane regions and following reduction of background signals. Additionally, we introduce an innovative approach utilizing optically-controlled phase separation for the detection and tracking of membrane lipids. The resultant improvements in biosensor performance surpass conventional tools, with the added potential for further enhancement through light simulation. This work not only contributes to the refinement of membrane biosensors but also holds promise for the design and optimization of other biosensor systems.