Design Rules for the Sequestration of Viruses into Polypeptide Complex Coacervates

Joshi, Pratik U.; Decker, Claire; Zeng, Xianci; Sathyavageeswaran, Arvind; Perry, Sarah L.; Heldt, Caryn L.

doi:10.1021/acs.biomac.3c00938

Cited by 3 publications

(4 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Encapsulationmentioning

confidence: 99%

See 1 more Smart Citation

Self-Assembling Polypeptides in Complex Coacervation

Sathyavageeswaran,

Bonesso Sabadini,

Perry

2024

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

Metrics & MoreArticle Recommendations CONSPECTUS: Intracellular compartmentalization plays a pivotal role in cellular function, with membrane-bound organelles and membrane-less biomolecular "condensates" playing key roles. These condensates, formed through liquid−liquid phase separation (LLPS), enable selective compartmentalization without the barrier of a lipid bilayer, thereby facilitating rapid formation and dissolution in response to stimuli.Intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs), which are often rich in charged and polar amino acid sequences, scaffold many condensates, often in conjunction with RNA.Comprehending the impact of IDP/IDR sequences on phase separation poses a challenge due to the extensive chemical diversity resulting from the myriad amino acids and post-translational modifications.To tackle this hurdle, one approach has been to investigate LLPS in simplified polypeptide systems, which offer a narrower scope within the chemical space for exploration. This strategy is supported by studies that have demonstrated how IDP function can largely be understood based on general chemical features, such as clusters or patterns of charged amino acids, rather than residue-level effects, and the ways in which these kinds of motifs give rise to an ensemble of conformations.Our laboratory has utilized complex coacervates assembled from oppositely charged polypeptides as a simplified material analogue to the complexity of liquid−liquid phase separated biological condensates. Complex coacervation is an associative LLPS that occurs due to the electrostatic complexation of oppositely charged macro-ions. This process is believed to be driven by the entropic gains resulting from the release of bound counterions and the reorganization of water upon complex formation. Apart from their direct applicability to IDPs, polypeptides also serve as excellent model polymers for investigating molecular interactions due to the wide range of available side-chain functionalities and the capacity to finely regulate their sequence, thus enabling precise control over interactions with guest molecules. Here, we discuss fundamental studies examining how charge patterning, hydrophobicity, chirality, and architecture affect the phase separation of polypeptide-based complex coacervates. These efforts have leveraged a combination of experimental and computational approaches that provide insight into molecular level interactions. We also examine how these parameters affect the ability of complex coacervates to incorporate globular proteins and viruses. These efforts couple directly with our fundamental studies into coacervate formation, as such "guest" molecules should not be considered as experiencing simple encapsulation and are instead active participants in the electrostatic assembly of coacervate materials. Interestingly, we observed trends in the incorporation of proteins and viruses into coacervates formed using different chain length polypeptides that are not well explained by...

show abstract

Section: Encapsulationmentioning

confidence: 99%

“…We tested the potential effects of particle size by comparing the trends of encapsulation as a function of chain length for proteins with those for viruses . Specifically, porcine parvovirus (PPV) and human rhinovirus (HRV) were incorporated into the same poly(lysine)/poly(glutamate) coacervate system.…”

Section: Encapsulationmentioning

confidence: 99%

Self-Assembling Polypeptides in Complex Coacervation

Sathyavageeswaran,

Bonesso Sabadini,

Perry

2024

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Complex coacervates are defined as phase-separated oppositely charged polyelectrolytes in a common solvent (typically water or other aqueous mixtures) . Complex coacervates have been extensively studied for their fundamental behavior, and in applications that leverage their behavior in aqueous media, including stabilizing and sequestering proteins and other biological entities, biomaterials, and underwater adhesives. − However, their utilization in membrane applications has received less attention. If oppositely charged polyelectrolytes can be dissolved in a common solvent, they can potentially be used in novel approaches for membrane manufacturing.…”

Section: Introductionmentioning

confidence: 99%

Amphiphilic Polyelectrolyte Complexes for Fouling-Resistant and Easily Tunable Membranes

Mazzaferro,

Grasseschi,

et al. 2024

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Commercial membranes today are manufactured from a handful of membrane materials. While these systems are well-optimized, their capabilities remain constrained by limited chemistries and manufacturing methods available. As a result, membranes cannot address many relevant separations where precise selectivity is needed, especially with complex feeds. This constraint requires the development of novel membrane materials that offer customizable features to provide specific selectivity and durability requirements for each application, enabled by incorporating different functional chemistries into confined nanopores in a scalable process. This study introduces a new class of membrane materials, amphiphilic polyelectrolyte complexes (APECs), comprised of a blend two distinct amphiphilic polyelectrolytes of opposite charge that self-assemble to form a polymer selective layer. When coated on a porous support from a mixture in a nonaqueous solvent, APECs self-assemble to create ionic nanodomains acting as water-conducting nanochannels, enveloped within hydrophobic nanodomains, ensuring structural integrity of the layer in water. Notably, this approach allows precise control over selectivity without compromising pore size, permeability, or fouling resistance. For example, using only one pair of amphiphilic copolymers, sodium sulfate rejections can be varied from >95% to <10% with no change in effective pore size and fouling resistance. Given the wide range of amphiphilic polyelectrolytes (i.e., combinations of different hydrophobic, anionic, and cationic monomers), APECs can create membranes with many diverse chemistries and selectivities. Resultant membranes can potentially address precision separations in many applications, from wastewater treatment to chemical and biological manufacturing.

show abstract

“…From random phase approximation theory and molecular dynamics simulations, random polyelectrolyte sequences are expected to have a dramatic effect on the cooperativity of Coulomb interactions between oppositely charged macromolecules. 54,55 While we do not dwell on polyelectrolyte phase behavior in this current work, compositional drift can potentially offer more fundamental understanding of the statistical distribution of charges in multimonomeric polymers, for not only gene therapy but also wastewater treatment/purification strategies, 56 viral vaccine formulation, 57 and enhancing viscoelastic response in coacervation. 58 Here, we hypothesize that blocky attributes of P1 and P3 (as well as their PEGylated analogs P4 and P6) can influence not only pDNA stabilization, but also blood plasma protein interactions, distinguishing them from random binary polyelectrolytes.…”

mentioning

confidence: 99%