Multiphasic Coacervates Assembled by Hydrogen Bonding and Hydrophobic Interactions

Abstract

Coacervation has emerged as a prevalent mechanism to compartmentalize biomolecules in living cells. Synthetic coacervates help in understanding the assembly process and mimic the functions of biological coacervates as simplified artificial systems. Though the molecular mechanism and mesoscopic properties of coacervates formed from charged coacervates have been well investigated, the details of the assembly and stabilization of nonionic coacervates remain largely unknown. Here, we describe a library of coacervate-forming polyesteramides and show that the water-tertiary amide bridging hydrogen bonds and hydrophobic interactions stabilize these nonionic, single-component coacervates. Analogous to intracellular biological coacervates, these coacervates exhibit "liquid-like" features with low viscosity and low interfacial energy, and form coacervates with as few as five repeating units. By controlling the temperature and engineering the molar ratio between hydrophobic interaction sites and bridging hydrogen bonding sites, we demonstrate the tuneability of the viscosity and interfacial tension of polyesteramide-based coacervates. Taking advantage of the differences in the mesoscopic properties of these nonionic coacervates, we engineered multiphasic coacervates with core−shell architectures similar to those of intracellular biological coacervates, such as nucleoli and stress granule-pbody complexes. The multiphasic structures produced from these synthetic nonionic polyesteramide coacervates may serve as a valuable tool for investigating physicochemical principles deployed by living cells to spatiotemporally control cargo partitioning, biochemical reaction rates, and interorganellar signal transport.

Water-Soluble Soft Nylons: Novel Class of Soft Matter Exhibiting LCST-type Thermo-Responsiveness

“…As shown in Figure 5, cloud points gradually increased by about 20 °C with decreasing polymer concentrations. These results are consistent with coacervate-type phase separation, where the intermolecular aggregation of polymers is less probable at lower concentrations [36][37][38]40,59] .…”

“…These observations can be explained by partial dehydration of the polymer chain inducing the aggregation of an aliphatic group to coacervation. We might conclude that the phase separation of N-Me-2,8 is a coacervatetype phase separation [36][37][38]40,59] . Subsequently, we examined the influence of polymer concentration on thermal behavior.…”

“…In modern polymer science, the development of novel thermo-responsive polymers and their applications in soft matter such as smart materials and biomedical materials became an important research area [23][24][25][26] . During over 50 years of soft polymer matter research, a vast number of amphiphilic aliphatic polymers [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] and their copolymers [42][43][44][45][46][47][48] related to PNIPAM have been synthesized and investigated to control their phase separation behavior and cloud points [49][50][51] . Although many reports documented the significance of hydrophilic/hydrophobic balance for LCST-type phase separation, their quantitative guideline remains unclear [20,35] .…”

Hydrogen Bonding-Driven Self-Coacervation of Nonionic Homopolymers for Stimuli-Triggered Therapeutic Release

“…Such behavior could be ascribed to partial, instead of complete, dehydration of the polymer chains; a substantial amount of water content inside the coacervate permits sufficient polymer chain mobility below the phase transition temperature. So, it is obvious that amide (polymer)–water–amide (polymer) bridging H-bonding (Scheme ) is crucial for the present self-coacervation system, as demonstrated recently by Joy’s group …”

Modulating Phase Behavior in Fatty Acid-Modified Elastin-like Polypeptides (FAMEs): Insights into the Impact of Lipid Length on Thermodynamics and Kinetics of Phase Separation

“…Cells use membraneless organelles to regulate the spatiotemporal flow of life-sustaining matter, energy, and information. − These systems are all-aqueous emulsions formed via liquid–liquid phase separation (LLPS) of biomacromolecules . Compared to synthetic water-in-water emulsions, − biological condensates exhibit a far greater degree of structural complexity and functional tunability . For instance, cells regulate the formation and properties of their biological condensates through post-translational modifications (PTMs), , achieving a level of precision that remains unmatched by synthetic systems .…”