optoDroplet provides new hopes for the treatment of protein-related diseases

In a study published in the December 29 issue of Cell, Professor Brangwynne of Princeton University developed a new tool called optoDroplet through recombinant proteins including recombinant horse proteins. This tool can analyze the physical and chemical changes in the self-assembly of membranous organelles and provide new hopes for the development and treatment of protein-related diseases by controlling the aggregation and dissolution of proteins.

The OptoDroplet is a technique that relies on photogenetics to change the behavior of proteins by exposure to light. The major component of the cell is water, and therefore it is substantially transparent. Researchers have shown that they can induce phase transitions by activating photoactivators and produce membraneless organelles. At the same time, they can simply turn off the lights to cancel the process. Increasing light intensity and protein concentration allowed the researchers to further control transformation. By altering these factors, they can determine when to form condensed liquid proteins, as well as solid-like protein aggregates that may be associated with the disease.

Using mouse and human cells, the research team spliced genes from the Arabidopsis light-sensitive protein, and blue exposure will lead to self-assembly of the protein. Proteins fused with a light-sensitive label are thought to drive phase transitions in living cells. The researchers found that they can light the protein to induce aggregation, mimicking naturally occurring in the cell condensation process. The team repeatedly made the protein to condense and then dissolve by turning on and off light. Even after many cycles, this process proved completely reversible. However, with high-intensity light or high concentrations of protein, the researchers created a semi-solid gel. These gels were initially reversible, but over time they solidified to form irreversible bulk agglomerates, similar to those found in some diseases.

An example is a protein called FUS. FUS protein is essential for cells: it helps to produce other proteins and repair damaged DNA. But a large number of mutations may make FUS protein become too sticky, leading to amyotrophic lateral sclerosis (ALS). This is a progressive and fatal neurodegenerative disorder in which the patient loses the ability to autonomously control his or her muscles and protein aggregates accumulate in nerve cells of ALS patients. These clumps may originate from the pathological aggregation of FUS or other proteins, rather than being maintained as a dynamic fluid. Huntington‘s disease and Alzheimer’s disease are also associated with protein clumps blocking cells, again demonstrating that abnormal phase transitions in cells are closely related to these protein concentrations and light intensities.

Professor Brangwynne looks forward to continuing to experiment with optoDroplet to better understand the complex behavior of cells. He also hopes that these insights will not only reveal how healthy cells work but also reveal how they are pathogenic and may ultimately cure the disease. Flarebio offers superior recombinant proteins like recombinant TLR2 at competitive prices for your research.