Researchers Use Optogenetics to Gain New Insights into Cellular Activity

Scientists from Princeton University have just discovered the mechanisms that keep cell organelles separated even when they lack membranes. The team used a newly developed tool called optoDroplet to examine and manipulate the matter inside living cells. The findings are in a paper that was just published in the journal Cell.

Cells are the building blocks of all living organisms, including humans. They contain a number of organelles, specialized subunits that have important functions such as generating energy, synthesizing proteins, and transporting materials. These organelles are separated from each other and the rest of the cell. Oddly, this is accomplished without membranes—the organelles are membraneless but somehow persist as separate structures. This cellular mystery has long puzzled scientists. Researchers now know that organelles use phase transitions (an example of a phase transition is water freezing into ice) to aggregate but the actual mechanisms were unknown.

A team of researchers used a tool called optoDroplet to manipulate living cells. The optoDroplet tool utilizes a technique called optogenetics to control cellular activity. In optogenetics, light-sensitive proteins can be manipulated by switching lights on and off. In the study, the team used optogenetics to induce phase transitions in living cells, allowing them to observe how the organelles behaved.

The researchers found that when activated, the proteins condensed and eventually formed solid-like gels. This process would begin when the optoDroplet light was switched on and could be stopped by switching the light off. After a certain point after activation, however, the gels became so condensed that they formed solid aggregates—which could damage the cell. Healthy cells have mechanisms in place to avoid this problem but the process might explain the dangerous protein aggregates found in Alzheimer’s disease and other disorders.

The team’s findings provide new insights into how organelles use phase transitions to aggregate and stay separated from other parts of the cell. The study also demonstrated the usefulness of optoDroplet tools, which can be used to study a number of complex cell processes. The team hopes to continue their research to better understand how cells operate at the molecular level.


Shin et al. Spatiotemporal Control of Intracellular Phase Transitions Using Light-Activated optoDroplets. Cell (2016).

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