Phase separation: Bridging polymer physics and biology

Abstract

Significant parallels exist between the phase separation behavior of polymers in solution and the types of biomolecular condensates, or 'membraneless organelles,' that are of increasing interest in living systems. Liquid-liquid phase separation allows for compartmentalization and the sequestration of materials, and can be harnessed as a sensitive strategy for responding to small changes in the environment. Here, I review many of the parallels and synergies between ongoing efforts to study and take advantage of phase separation in living vs. synthetic materials.

Recent progress in the science of complex coacervation

“…18,21,[242][243][244][245][246][247][248][249][250][251] Here, the ability of biology to precisely tune the sequence of monomers along proteins and other biomacromolecules seems to play a key role in biological function, even in highly disordered systems similar to the types of polymer solutions found in non-biological coacervation. 4 Understanding and mimicking these systems has thus become an active area of research, due not only to the impliciations in biophysics, but in a more fundamental aspiration to control polymer structure and function via monomer sequence. 252…”

“…Charged soft matter is ubiquitous in both the synthetic and natural worlds, where the presence of electrostatic interactions serves as a way to imbue systems with the ability to respond to stimuli and enrich the possibilities for self-assembly. 1 In this review, we consider a class of charged materials -complex coacervatesthat has emerged over the past few decades as particularly versatile, 2,3 being found as a common interaction motif in biology, 4 while simultaneously being widely used in the chemical industry as a functional material in personal care products and foods. [5][6][7] The widespread relevance of coacervates has led to a recent surge of research over the past decade, which has led to new fundamental scientific concepts, next-generation functional (bio)materials, and has set the stage for a new wave of modern materials that is pushing the boundaries of polymer physics and chemistry.…”

Sequence-dependent self-coacervation in high charge-density polyampholytes

“…[19][20][21][22][23][24] Recently, there has been great interest in understanding the critical role IDPs play in the formation of membraneless organelles through a liquid-liquid phase separation process. [24][25][26][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] The solution properties that lead to solution demixing in IDPs are encoded within the sequence of the protein. 9,32,46,47 Post-translational modifications can also lead to phase separation in IDPs, for instance phosphorylation of residues along the polypeptide chain can change the electrostatic interactions leading to demixing.…”

“…[62][63][64][65] Inspired by this connection, polyampholyte phase separation is sometimes called self-coacervation. 62,63 Complex coacervation itself has also been used as a polymer analogy to IDP-based phase separation in biological systems; 33 indeed, the physical understanding of coacervate physics developed by the community has striking similarities to the development of polyampholyte physics. The earliest work in this area combined Flory-Huggins theory of polymer mixing with the Debye-Hückel theory of dilute electrolytes, 66 resulting in the Voorn-Overbeek model.…”

Liquid–Liquid Phase Separation: Undergraduate Labs on a New Paradigm for Intracellular Organization

“…Thermodynamics lays the foundation for us to describe the necessary conditions and driving forces for LLPS (17). Models from the field of polymer physics capture essential features of LLPS with a minimum of parameters (4,20). From the fields of fluid dynamics and soft matter physics, we borrow tools to understand the material properties of these MLOs (38).…”