Macro- and Microphase Separated Protein-Polyelectrolyte Complexes: Design Parameters and Current Progress

Abstract

Protein-containing polyelectrolyte complexes (PECs) are a diverse class of materials, composed of two or more oppositely charged polyelectrolytes that condense and phase separate near overall charge neutrality. Such phase-separation can take on a variety of morphologies from macrophase separated liquid condensates, to solid precipitates, to monodispersed spherical micelles. In this review, we present an overview of recent advances in protein-containing PECs, with an overall goal of defining relevant design parameters for macro- and microphase separated PECs. For both classes of PECs, the influence of protein characteristics, such as surface charge and patchiness, co-polyelectrolyte characteristics, such as charge density and structure, and overall solution characteristics, such as salt concentration and pH, are considered. After overall design features are established, potential applications in food processing, biosensing, drug delivery, and protein purification are discussed and recent characterization techniques for protein-containing PECs are highlighted.

Temperature, Hydrostatic Pressure, and Osmolyte Effects on Liquid–Liquid Phase Separation in Protein Condensates: Physical Chemistry and Biological Implications

“…Knowledge of the LLPS behavior of proteins as af unction of all thermodynamic variables, including pressure, is of directr elevance to recent efforts to designp roteinlike heteropolymer sequences with novel materials properties, including desirableL LPS behaviors. [36,[65][66][67][68][69][70]169] In ab roader technological context,s uch knowledge is also essential in areass uch as protein crystallization (LLPS occurs generally under conditions where the protein is metastablew ith respectt oc rystallization), protein purification, formulation development for therapeutic proteins (including the possibility of operating at industrial scales larger than other relatedt echniques as ultrafiltration, drying,c hromatography,a nd dialysis), and high-pressuref ood processing. [2,3,49,73,74,[196][197][198] It is hoped that the present summary of the initial yetpromising findings on pressure effects on biomolecular condensates will spur more efforts in this exciting area of interdisciplinary research.…”

“…novel materials properties. [36,[65][66][67][68][69][70] Knowledge of the phase behavior of proteins is also essential in areas such as protein purificationa nd long-term storagea sw ella sf or high-pressure food processing. [2,45,49,[71][72][73][74] Taking ab asic step in our endeavor to better understand biomolecular LLPS, our focus here is on the equilibrium thermodynamics for the fundamental physical insights it offers, withoutl osing sight of the fact that biologically functional condensates are, in many respects, highly complex "active liquids" [40,75] regulated by chemical reactions, posttranslational modifications, and other non-equilibrium processes.…”

Assembly and Characterization of Polyelectrolyte Complex Micelles

“…The resulting self-assembled core-shell nanoparticles are variously referred to as polyelectrolyte complex micelles (PCMs), polyion complex micelles, block ionomer complexes, or coacervate-core micelles by analogy to surfactant micellization, even though all components of the system are hydrophilic 6,7 . PCMs' ability to encapsulate hydrophilic molecules such as proteins and nucleic acids, as well as the extensive tunability offered by the block copolymer carrier architecture makes them attractive candidates for delivering therapeutic molecules in vivo [8][9][10][11][12][13] .…”

Effect of Pollyallylamine on Alcoholdehydrogenase Structure and Activity

“…There are a number of works in the literature that solve similar problems and show various options for complexation and the effect of polyelectrolyte on protein [10][11][12]. Thus, in the work of Durdenko et al, the effect of inorganic monovalent and divalent salts on the complexation of the PAA polycation with the urease enzyme was studied.…”