Protonation-driven phase separation and self-assembly of amine containing polyelectrolytes

Coacervate droplets serve as synthetic counterparts to membrane-less organelles and have been widely used as model systems to study fundamental processes in protocells. These droplets exhibit key cellular properties such as molecular uptake, enzymatic catalysis, and selective partitioning. However, to better mimic biological systems, coacervates must incorporate dynamic features that drive higher-order self-assembly. Such dynamics are crucial for understanding aggregation-driven fibrillation processes, which play a role in neurodegenerative diseases.

In our work, we present a minimalistic system consisting of a single type of polymer chain in an aqueous solution. Upon the addition of mineral acids, these polymers form dynamic coacervate droplets that gradually evolve into higher-order fibrillar structures. This transformation is driven by a combination of counterion condensation, hydrophobic interactions between polymeric moieties, and, most importantly, a pH/polarity gradient within the metastable coacervate droplets. Over time, these factors facilitate a slow morphological transition, leading to the formation of robust fibrillar assemblies.

Furthermore, we investigated the influence of these amine-based assemblies on polymer transfection efficiency. We also demonstrated that the system can be made light-responsive by attaching suitable fluorophores to the unassembled polymer chains. Our study challenges the conventional understanding that coacervate formation requires the complexation of oppositely charged polyelectrolytes. It also provides insights into the maturation and aging processes in synthetic protocells, opening new avenues for research into self-assembling biomimetic systems.

References:

(1)       Jain, M.; Seth, J. R.; Hegde, L. R.; Sharma, K. P. Unprecedented Self-Assembly in Dilute Aqueous Solution of Polyethyleneimine: Formation of Fibrillar Network. Macromolecules 2020, 53 (20), 8974–8981. https://doi.org/10.1021/acs.macromol.0c01501.

(2)       Sharma, S.; Sharma, K. P. Light-Responsive Self-Assembled Microstructures of Branched Polyethyleneimine at Low pH. Chem. Commun. 2022, 58 (99), 13779–13782. https://doi.org/10.1039/D2CC04996A.