Session B31: Polyelectrolyte Complexation II: Structure and Dynamics

Robust and Tough Wet Adhesives based on Polyelectrolyte Complex Hydrogels

Significant advances in emulating natural glues have led to a diversity of wet adhesive chemistries. However, most current adhesives cure slowly in unprotected aqueous environments, leading to precursor deactivation, dilution, and weak adhesion. In this talk, I will discuss our progress in developing robust wet adhesives based on polyelectrolyte complex-interpenetrating network (PEC-IPN) hydrogels. These hydrogels are fabricated by curing polymeric adhesive precursors in protected environments provided by self-assembled polyelectrolyte complex (PEC) hydrogels, thus mitigating precursor dilution. In the resulting PEC-IPN hydrogels, the PEC network also features a mesoscale hierarchical structure, contributing to the adhesives' superior mechanical and adhesive performance. Model PEC-IPN hydrogels comprising a PEC network composed of oppositely charged block polyelectrolytes and a covalently crosslinked tetra-PEG network will be demonstrated to serve as a material platform for robust and tough wet adhesives. X-ray scattering investigations will establish the persistence of the PEC network upon the inclusion of tetra-PEG chains in it and their subsequent photocrosslinking. Simultaneously, marked improvements in shear and tensile strengths of PEC-IPN hydrogels upon incorporating the covalent tetra-PEG network, even as a minor component, will be demonstrated. Precise tuning of microstructure and shear moduli of the hydrogels prior to the formation of covalent networks, and of the shear and tensile strength, toughness, and swelling characteristic in the IPN hydrogels will be highlighted.   

Relaxation Times of Solid-like Polyelectrolyte Complexes of Varying pH and Water Content

The effect of complexation pH and water on the relaxation time and dynamics of polyelectrolyte (PE) complexes (PECs) and coacervates remains poorly understood. Here, we describe the dynamic mechanical behavior of solid-like PECs containing weak PEs poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) at varying complexation pH, relative humidity, and temperature with support from molecular dynamics simulations. Time−temperature, time−water, and time−intrinsic ion pair superposition principles are applied to obtain the relaxation times. It is shown that the natural log of relaxation time in hydrated PAH/PAA PECs is inversely proportional to the volume fraction of water (ln τ ∼ ϕ_w ⁻¹ ) for a given complexation pH. For all complexation pH values examined, the natural log of relaxation time collapsed into a single line when plotted against the ratio of the number of intrinsic ion pairs to water molecules (ln (τ) ∼ number of intrinsic ion pairs/ number of water molecules). Taken together, this suggests that the relaxation of solid-like, hydrated PAH/PAA PECs is mediated by bound water at the intrinsic ion pair.   

Polyelectrolyte complexation in brushes

Anionic polystyrene sulfonate (PSS) chains were grafted from mica surfaces to create dense brushes for use in surface force (SFA) measurements. These surfaces were mounted in the SFA embedded in an aqueous solution environment of low ionic strength into which the cationic homopolymer, poly[(vinylbenzyl) trimethylammoniumnitrate] (PVBTMAN), is introduced. Before the introduction there are long range repulsive forces between the PSS brushes as we have frequently documented before. Interestingly, the introduction of PVBTMAN initially produces an increase in the range of the purely repulsive forces. However, with addition of a further amount of PVBTAN and/or additional waiting time under compression, the range of the forces shrinks and attractive forces appear on separation. These different stages appear to arise from different stages of penetration of the cationic homopolymer into the anionic brush.    

Brushing Up on Coacervates: How Chain Anchoring Can Incorporate Solid Particles into Fluid Polyelectrolyte Complexes

When charged solid particles are combined with an oppositely charged polyelectrolyte in an aqueous suspension/solution, Coulombic attractions (and counterion release) drive polymer adsorption and intractable (kinetically-trapped) particle aggregation.  In contrast, combination of two oppositely charged polyelectrolytes in aqueous solution often forms a fluid complex (“complex coacervate”) described by an equilibrium thermodynamic phase diagram in which salt concentration appears as a temperature variable.  We attach the chain ends of a polyanion oligomer to nanoparticles and form complex coacervates upon addition of a polycation.  The work probes the numbers and concentrations of tethered chains in the polyanion brush needed to facilitate solid nanoparticle incorporation into the coacervate.  We find that without sufficient bound chains, aggregates rather than a complex coacervate is formed.   

Computational Study of Isotropic-to-Nematic Transition in Salt-Free Coacervates

Complex coacervation between oppositely charged polyelectrolytes (PEs) has attracted considerable interest because it serves as a model of intracellular compartmentalization and early stage prebiotic evolution. Recent experimental and theoretical studies have found this phase separation can be accompanied by the liquid crystal ordering (LCO) within the coacervate phase over limited ranges of flexibility of the PE chains (e.g. double-stranded DNA). Our work uses molecular dynamics simulations to demonstrate the existence of the isotropic-to-nematic transition in salt-free coacervates as the stiffness of the semiflexible chains increases. Two particular cases of coacervates are considered: (i) oppositely charged semiflexible PEs and (ii) semiflexible polyanions and flexible polycations. By comparing coacervates with the corresponding solutions of neutral polymers, we show that electrostatic interactions in coacervates facilitate LCO, in accordance with our earlier theoretical predictions. Our simulations also reveal that, near the interface between the nematic coacervate and supernatant phases, PEs prefer to be aligned parallel to the interface. This work provides molecular-level insight into the physics of intra-coacervate LCO and the role of Coulomb interactions in these systems.   

Effect of Charged Block Length Mismatch in Double Diblock Polyelectrolyte Complex Micelles

When two oppositely charged hydrophilic block polyelectrolytes are mixed, they can spontaneously self-assemble into micelles with polyelectrolyte complex (PEC) cores and hydrophilic coronas. These polyelectrolyte complex micelles (PCMs) are responsive to salt, temperature and pH, which makes them attractive carriers for hydrophilic cargo in biological applications. It is commonly assumed that the charged block lengths of the constituent diblocks must be identical for assembly to occur. In our work, we explore the role of charged block length mismatch in PCMs through a series of model diblocks with a wide range of block asymmetries. We use a combination of small-angle x-ray scattering and dynamic light scattering to measure the core size and hydrodynamic radius of our PCMs, which allows us to connect molecular features to PCM structural characteristics. Our results provide guidelines for the development of asymmetric PEC assemblies both in PEC gels and PCMs.   

Molecular Design of Oligonucleotide Polyelectrolyte Complex Micelles

Developing effective non-viral methods for delivery of nucleic acids and other macromolecular therapeutics is one of the most pressing challenges in nanomedicine. The immense potential of engineered nucleic acids as therapeutic agents is limited by the difficulty of overcoming physical and biological barriers. A solution to this critical problem is using hydrophilic charged block polymers to condense nucleic acids, driving nanoscale phase separation to form polyelectrolyte complex micelles (PCMs). These core-shell nanoparticles sequester and protect nucleic acids from nucleases and immune response. Still, few systematic studies have been conducted on how parameters such as nucleic acid backbone chemistry, polymer charge density and polymer length influence PCM properties, despite evidence that these strongly influence complexation behavior. Here, I will discuss our investigations of the impact of physical and chemical properties of each polyelectrolyte on complex assembly using small angle X-ray scattering, dynamic light scattering, and electron microscopy. We find the physical size and molecular structure of the nucleic acid backbone and cationic charged group strongly influence complexation behavior and stability and have determined scaling behaviors for micelle size and aggregation number. These observations narrow the design space for tailored therapeutic micelles and provide new insights into the physics of polyelectrolyte self-assembly.   

Stable Membraneless Complex Coacervate Microdroplets

Complex coacervation is the phenomenon of liquid-liquid phase separation driven by electrostatic association of oppositely charged multivalent macromolecules in aqueous media, creating coacervate microdroplets enriched with charged moieties. These membraneless microdroplets possess numerous attributes desired in lipid-free protocell models and colloidal bioreactors, including spontaneous self-assembly leading to compartmentalization, stability across a wide range of physiochemical conditions (temperature, pH, and ionic strength), and crowded environments that mimic the interior of cells. Moreover, the self-assembly processes that drive coacervation result in highly selective sequestration of (bio)molecules into the crowded coacervate environments. Concomitantly, the membraneless coacervate-water interface facilitates rapid transport of small molecules, resulting in significant acceleration of bioreactions in coacervate microdroplets. However, the membraneless coacervate-water interface that facilitates many of the bio(techno)logical functions of the coacervate microdroplets also facilitates their coalescence, resulting in their rapid coarsening. In this presentation, we will demonstrate our progress on stabilization of complex coacervate microdroplets composed of oppositely charged homopolyelectrolytes by addition of anionic comb polyelectrolytes. We will also demonstrate tunability of microdroplet size and show that the droplets remain stable in solution for several months and can withstand high ionic strength environments. Furthermore, we will demonstrate strong partitioning of proteins into these droplets accompanied by an up to 10-fold increase in enzyme-mediated bioreaction rates. Due to the low cost of the constituent polymers, these results will be argued to pave the way for the use of stabilized coacervate dispersions as economical, large-scale bioreactors.   

Multiphase Complex Coacervate Droplets from Two-Polyelectrolyte Systems

Microscale inhomogeneous polyelectrolyte complexes have been shown to form in coacervates from three or more polyelectrolyte components, as “protocells” with fatty acid, lipid, or protein adsorbed to the surface of a two-protein condensate droplet, or upon application of an electric field or a laser tweezer. Recently, we found that a transient internal microstructure can form in systems of only two polyelectrolytes via internal interfacial relaxation of aggregated complexes, and that this morphology is highly sensitive to the details of mixing and flow. Here, we report formation of protocell-like core-shell coacervates formed in a two-polyelectrolyte system, in cases of extreme non-stoichiometric mixing of the polyanion and polycation. We characterize where the transition from single to multiple emulsion coacervation occurs as a function of relative concentration of the two polyelectrolytes and salt, polyelectrolyte identity, and the mixing approach, and identify the compartmentalization of phases and chemical components of the multiple emulsion. We also discuss the metastability of the structures, and the possibility of using more complicated mixing protocols to form even more complicated structures using just two polyelectrolytes.   

Molecular Exchange Kinetics in Complex Coacervate Core Micelles:Role of Associative Interaction

Complex coacervate core micelles (C3Ms) have been investigated in a wide range of applications owing to stimuli-responsiveness and hydrophilic cores. Compared to structure and morphology, much less is known about the kinetics of C3Ms, yet the fundamental understanding is essential for micelle stability, reproducibility, and structure design. In this study, we investigated the equilibrium exchange dynamics between C3Ms characterized by time-resolved small-angle neutron scattering (TR-SANS) measurement. A pair of well-defined poly(ethylene oxide-b-allyl glycidyl ether) (PEO-PAGE) was synthesized and functionalized with charged moieties including guanidinium (G), ammonium (A), and sulfonate (S); one with a normal PEO, and the other with a fully deuterated PEO. C3Ms with hydrogen/deuterium labeling were prepared by simple mixing of two oppositely charged hPEO-PAGE or dPEO-PAGE solutions, respectively. Strong dependence of the exchange rates on the salt and ion pair revealed that the coacervate core dynamics is crucial. Proposed relaxation model with sticky-Rouse dynamics and thermodynamic barrier for chain expulsion captures the relaxation behavior of C3Ms.   

Local Segmental Dynamics of Polyelectrolyte in Complex Coacervates

Complex coacervates (CC) are polymer-rich liquid phase generated when two oppositely charged polyelectrolytes are mixed in aqueous solutions. Dynamics of CC has mostly been studied by rheology, probing relaxation times on multiple length scales such as reptation, entanglement and ion-pair rearrangement. However, there are still limited information on local segmental dynamics that correspond to angstrom-scale. In this study, the segmental dynamics of CC are revealed as a function of salt concentration by quasi-elastic neutron scattering (QENS). Model polyelectrolytes functionalized with ammonium, guanidinium and sulfonate groups were synthesized by anionic ring-opening polymerization and post-modification. QENS results show that the amount of unpaired segments in ammonium-based coacervates is increased and their segmental dynamics are enhanced with salt concentration. In stark contrast, guanidinium-based coacervates show slower segmental dynamics and their amount is independent of the salt concentration.   

Self-ordering in a 2D two-component system modelling the behavior of a mixture of two oppositely charged polyelectrolytes

A possible self-ordering mechanism in a mixture solution of two oppositely charged polyelectrolytes, is discussed. In the case of strongly charged polyelectrolytes, the electrostatic interaction of oppositely charged macromolecules results in formation of neutral complexes (ladders or scrambled-eggs). At low concentrations, these complexes are not connected each other, forming a suspension-like system. However, if the ionization level of the one of these polyelectrolytes is enough low (whereas the other one remains strongly charged), only charged monomers of the weakly charged polymer will form the coupled pairs with the oppositely charged monomers of strong polyelectrolyte. In such a case, the bridging phenomenon can be observed when the macromolecules of the weakly charged polymer can form reversible bonds with different macromolecules of strongly charged polyelectrolyte, playing a role of tie molecules. As a result, a percolated macromolecular network arises. Note that such a network can be formed even at low polymer concentrations corresponding to dilute solutions of neutral polymers. The above macromolecular network was analyzed in 2D case with the help of a relatively simple lattice model consisting of identical quantity of two types springs having different elasticities and equilibrium lengths. It turned out that such a system can demonstrate an orientational self-ordering when most springs of the one type will be orientated along one direction (for example, along x-axis), whereas most springs of other type will be orientated along other direction (along y-axis). The reorganization of the disordered system into the ordered one (and back) occurs, for example, under variation of the ionization level of weakly charged polymer by variation in the system pH. The surprised peculiarity of the model in question is that the system cross-over to the ordered state can occur as a phase transition both of the first and second kind depending on the system parameter values.