Experimental model systems for living cells provide a route to study the physicochemical behavior of the cell while eliminating some of the inherent biocomplexity. A number of membraneless organelles that exhibit liquid-like behavior (e.g. nucleoli, P granules, and Cajal bodies) have recently been discovered, making coacervation of biopolymers into a dense polymer-rich liquid phase an attractive model for these organelles.  However, coacervation alone does not capture key aspects of the intracellular environment. The cellular milieu contains a wide variety of macromolecules that combine to make up ~30 wt.% of the cell, leading to a macromolecularly crowded solution. Crowding can significantly impact biomolecular structures and interactions, making it an important consideration in experimental model systems. Investigation of coacervation in the presence of varying crowders and their small molecule analogues provides insight into the ways in which the crowded intracellular environment may impact liquid-liquid phase separation (LLPS). The numerous membraneless organelles that exist within cells each have unique biopolymer content and function, and may form via different LLPS mechanisms. These membraneless compartments are utilized alongside membrane-bound organelles to localize and modulate bioactivity. The combination of coacervation, both simple and complex, with neutral polymer aqueous phase separation mimics the variety of liquid microcompartments that can exist in living cells. Encapsulation of coacervate systems within membrane-bound vesicles provides additional complexity to the cellular mimic. This work makes coacervation-based model systems for intracellular organization more accurate through the incorporation of macromolecular crowding, neutral polymer aqueous phase separation, and membrane-bound compartments.

Coacervation-based model systems for intracellular compartmentalization

256th National Meeting (2018)

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