Phase-Separating Aqueous Polymer Solutions as Simple Experimental Models for Cytoplasm

Abstract

The interior of biological cells is crowded with macromolecules, heterogeneous in composition, and dynamic. We are developing simple experimental models for intracellular environments based on aqueous polymer solutions. Macromolecular crowding is modeled by inclusion of polymers such as polyethylene glycol or dextran; when both polymers are present aqueous phase separation can occur. Phase separation provides microcompartments corresponding to the dextran-rich and PEG-rich phase domains and enables control over the local concentration of not only the polymers themselves but also any molecules that accumulate in one of the phases by partitioning. Local enrichment of tenfold or greater can be maintained between the phases for solutes such as nucleic acids or proteins, and can be used to drive reactions that are concentration-dependent. Encapsulation of the aqueous two-phase systems within lipid vesicles having a semipermeable membrane provides a primitive model of biological cells capable of microcompartmentation, polarity, and asymmetric division. The synthesis and characterization of artificial cells and cell-like environments may provide new insight into how fundamental chemical and physical phenomena common to all cells may have shaped the development of early cells and underlie many of the seemingly complex behaviors of modern cells.