PT  - JOURNAL ARTICLE
AU  - Cesar L Cuevas-Velazquez
AU  - Tamara Vellosillo
AU  - Karina Guadalupe
AU  - H Broder Schmidt
AU  - Feng Yu
AU  - David Moses
AU  - Jennifer AN Brophy
AU  - Dante Cosio-Acosta
AU  - Alakananda Das
AU  - Lingxin Wang
AU  - Alexander M Jones
AU  - Alejandra A Covarrubias
AU  - Shahar Sukenik
AU  - José R Dinneny
TI  - Intrinsically disordered protein biosensor tracks the physical-chemical effects of osmotic stress on cells
AID  - 10.1101/2021.02.17.431712
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.17.431712
4099  - http://biorxiv.org/content/early/2021/02/18/2021.02.17.431712.short
4100  - http://biorxiv.org/content/early/2021/02/18/2021.02.17.431712.full
AB  - Cell homeostasis is perturbed when dramatic shifts in the external environment cause the physical-chemical properties inside the cell to change. Methods that dynamically monitor these intracellular effects are currently lacking. Here, we leveraged the environmental sensitivity and structural plasticity of intrinsically disordered regions (IDRs) to develop a FRET biosensor capable of monitoring rapid intracellular changes caused by osmotic stress. The biosensor, named SED1, utilizes the Arabidopsis intrinsically disordered AtLEA4-5 protein expressed in plants under water deficit. Computational modeling and in vitro studies reveal that SED1 is highly sensitive to macromolecular crowding. SED1 exhibits large and near-linear osmolarity-dependent changes in FRET inside living bacteria, yeast, plant, and human cells, demonstrating the broad utility of this tool for studying water-associated stress. This study demonstrates the remarkable ability of IDRs to sense the cellular environment across the tree of life and provides a blueprint for their use in environmentally-responsive molecular tools.Competing Interest StatementThe authors have declared no competing interest.