Biophysical-to-DNA Catalytic Cumulative Birecorder for Measuring Continuous Membrane Fluidity

Abstract

Recording biophysical processes is crucial to understanding the cellular history and stimuli-responsive behaviors. The construction of memory machines for continuous membrane fluidity, however, remain challenging. Here, we report a biophysical-to-DNA catalytic cumulative birecorder (BioDIMER) for making individual recordings of continuous membrane fluidity events into both fluorescent signals and DNA unique molecular identifiers (UMIs) sequencing. We do this through engineered DNAzyme probe sets that accumulate bimodal signals responsive to each transient encounter on cell membrane. This in situ imaging captures spatiotemporal information, and the UMIs sequencing counts the number of transient encounters over time by digital quantification. The DNA catalytic bimodal signals enable continuous records of new events without corrupting the records of older events and achieve multidimensional interpretation of membrane fluidity timing. Using this proof-of-concept method, we recorded and deciphered differential cell membrane dynamics across diverse cell types and states, including cell cycle phases, cardiac hypertrophy, myotube differentiation, and cellular senescence. We found the first decreased and then increased change of membrane fluidity during the cell circle phases. In cardiac hypertrophy, we visualized an enhanced membrane fluidity. Oppositely, cellular senescence caused a significant reduction in membrane fluidity. They implied a highly dynamic organization of cell membrane components.

Affiliated Institutions

• Xi'an Jiaotong University CN
• Frontier Science Foundation CH
• Institute of Science and Technology

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