Polyampholyte physics: Liquid–liquid phase separation and biological condensates

Current Opinion in Colloid & Interface Science · 2021 · 72 citations

• Computer Science
• Physics
• Materials science

Polymersomes Decorated with the SARS-CoV-2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity

ACS Central Science · 2021 · 37 citations

• Cell biology
• Virology
• Computational biology

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle. We evaluated the vaccination efficacy of these surface-decorated polymersomes (RBD_surf) in mice compared to RBD-encapsulated polymersomes (RBD_encap) and unformulated RBD (RBD_free), using monophosphoryl-lipid-A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBD_surf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBD_surf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBD_surf and RBD_encap drove similarly robust CD4⁺ and CD8⁺ T cell responses that produced multiple Th1-type cytokines. We conclude that a multivalent surface display of spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.

Polyelectrolyte Complex Coacervation across a Broad Range of Charge Densities

Macromolecules · 2021 · 136 citations

• Chemical physics
• Materials science
• Chemistry

≤ 0.25. Preferential salt partitioning to either coacervate or supernatant was found to be dictated by the chemistry of the constituent (co)polyelectrolytes.

Effect of Solvent Quality on the Phase Behavior of Polyelectrolyte Complexes

Macromolecules · 2020 · 94 citations

• Chemistry
• Chemical physics
• Polymer chemistry

The role of polyelectrolyte–solvent interactions, among other non-Coulomb interactions, in dictating the thermodynamics and kinetics of polyelectrolyte complexation is prominent yet sparingly studied. In this article, we present systematic comparisons of the binodal phase behavior of polyelectrolyte complexes (PECs) comprising polyelectrolytes with varying quality of backbone–solvent interactions. Experimental phase diagrams of polyelectrolyte complexes with either a peptide or an aliphatic backbone highlight the influence of backbone chemistry on the compositions of complexes and their salt resistance. Corresponding theoretical phase diagrams, obtained from a framework combining the random phase approximation and the Flory–Huggins approach, reveal a transition from closed phase boundaries, with confined two-phase regions for PECs in good solvents, to open phase boundaries, wherein two-phase systems are predicted to exist even at very high salt concentrations, for PECs in poor solvents. These predicted trends compare qualitatively well with experimental observations of low salt resistance (∼1 M NaCl) of PECs comprising hydrophilic polyelectrolytes and persistence of complexes, stabilized by short-range hydrophobic interactions, even at very high salt concentrations (∼6 M NaCl) for PECs comprising hydrophobic polyelectrolytes.

Impact of wet-dry cycling on the phase behavior and compartmentalization properties of complex coacervates

Nature Communications · 2020 · 86 citations

• Biophysics
• Chemistry
• Biology

Abstract Wet-dry cycling on the early Earth is thought to have facilitated production of molecular building blocks of life, but its impact on self-assembly and compartmentalization remains largely unexplored. Here, we investigate dehydration/rehydration of complex coacervates, which are membraneless compartments formed by phase separation of polyelectrolyte solutions. Solution compositions are identified for which tenfold water loss results in maintenance, disappearance, or appearance of coacervate droplets. Systems maintaining coacervates throughout the dehydration process are further evaluated to understand how their compartmentalization properties change with drying. Although added total RNA concentrations increase tenfold, RNA concentration within coacervates remains steady. Exterior RNA concentrations rise, and exchange rates for encapsulated versus free RNAs increase with dehydration. We explain these results in light of the phase diagram, with dehydration-driven ionic strength increase being particularly important in determining coacervate properties. This work shows that wet-dry cycling can alter the phase behavior and protocell-relevant functions of complex coacervates.