“Using DNA Nanostars to Model Phase Separation”
Phase separation is when liquids demix into two different populations, like oil and water. Both the formation of membrane-less compartments and development neurodegenerative diseases involve protein phase separation, which has macroscopic behaviors influenced by the number and strength of interactions. Because it is experimentally difficult to tune these parameters using proteins, we use DNA as a simplified, microscopic model to show how they influence phase separation.
We designed “DNA nanostars” with multiple double-stranded “arms” that stick out from the center and bind to other arms of neighboring DNA nanostars using self-complementary, single-stranded “hands”. We examined the concentrations of these two phases as a function of binding strength (concentration of salt in solution) and valence (number of nanostar arms).
Results show that raising salt concentration increases the DNA dense phase concentration, indicating a decrease in space between DNA nanostars, due to decreased repulsion, and an increase in occupied hands from increased binding strength. Increasing valence expands the range of phase-separating salt concentrations and the DNA concentration in the dense phase, suggesting an increase in the fraction of bound DNA nanostars.
Discovering which conditions are most favorable for DNA phase separation will inform which type of protein shapes will phase separate. This new knowledge of phase separation may help us better understand the mechanisms and conditions of neurodegenerative diseases.
SMURF (Summer MRSEC Undergrad Research Fellowship)