Genetically encoded systems for cytosolic activity recording and molecular archiving across time

Abstract

Cellular functions are governed by dynamic changes in molecular abundance, state, activity, and interactions within the cytosol. Current molecular tape recorders leverage nuclear transcriptional programs in eukaryotic cells to provide scalable readout of gene regulation dynamics, but cytosolic activity, molecular abundance, and state remain inaccessible. Here, we introduce CyTRACE, a genetically encoded, scalable framework for cytosolic activity recording and molecular archiving across time. CyTRACE ventures beyond the cell nucleus, deploys cytosol-localized protein tape monomers as direct activity sensors and molecule catchers, and offers physiological sensitivity, spatiotemporal resolution, and programmability. Within this modular framework, CytoSense records protease and kinase signaling activities while CytoCatch archives cytosolic proteins, each with temporal continuity in single mammalian cells. CyTRACE thus opens cytosolic biology to scalable activity readout and molecular interrogation.