Coupling liquid phases in 3D condensates and 2D membranes: Successes, challenges, and tools

This review describes the major experimental challenges researchers meet when attempting to couple phase separation between membranes and condensates. Although it is well known that phase separation in a 2D membrane should affect molecules capable of forming a 3D condensate (and vice versa), few researchers have quantified the effects to date. The scarcity of these measurements is not due to lack of intense interest or effort in the field. Rather, it reflects significant experimental challenges in manipulating coupled membranes and condensates to yield quantitative values. These challenges transcend many molecular details, which means they impact a wide range of systems. This review highlights recent exciting successes in the field, and it lays out a comprehensive list of tools that address potential pitfalls for researchers who are considering coupling membranes with condensates.