Designing Cell-Like Microreactors through Bio-Inspired Compartmentalization

Biological cells provide an extraordinary model of an ideal "chemical factory" in which a large number of reactions take place simultaneously in an aqueous environment, with high efficiency and minimal interference. What can we learn from cells to improve the way we do chemistry in the lab? Cells organize their chemistry in space and time using biological compartments such as lipid vesicles, protein aggregates, and biocondensates. Our research focuses on creating synthetic versions of these compartments to develop cell-like systems for catalysis. This is done by localizing, stabilizing, and compatibilizing different catalysts through the use of biomimetic compartments. Our group has been working on biomimetic compartments derived from polymer vesicles and coacervates formed from polyelectrolytes and short peptides. In recent years, we’ve shifted our primary focus toward coacervates due to their versatility and their ability to mimic essential cellular features, such as molecular crowding and adaptive morphology and tunable chemical composition. Specifically, we are developing microreactors containing both biocatalysts (enzymes) and less commonly explored chemocatalysts, including transition metal catalysts, organocatalysts, and photocatalysts.

A breakthrough in extending microreactors beyond enzymes was the discovery that very short peptides (di- and tripeptides) can form coacervates with a unique hydrophobic microenvironment. This microenvironment has the remarkable ability to encapsulate, localize and stabilize hydrophobic chemocatalysts. Therefore, catalysts that are unsuitable for aqueous environments due to low solubility and stability in water can become active and compatible in aqueous environments when encapsulated within the microenvironment provided by the peptide coacervate. Furthermore, the design of distinct coacervate-based microreactors allows us to combine otherwise incompatible catalysts in the same system, such as enzymes and transition metal catalysts. This bio-inspired strategy offers a powerful solution to compatibility challenges for a wide range of catalysts, all in an aqueous medium.

In this lecture, I will discuss our recent advances in peptide-based coacervates, covering the synthesis and design principles of short peptides that undergo coacervation, their properties, and their applications in creating microreactors for chemo- and biocatalysis in aqueous environments. In addition, I will discuss how our lab is developing stimuli-responsive copolymers and peptides to construct compartments with adaptive permeability, controlled self-assembly, and dynamic morphology.