Dynamic Covalent Boronate Chemistry for In Situ Formation, Interfacial Stabilization, and Cytomimetic Optimization of Coacervates

TL;DR

This paper introduces a new method using dynamic covalent chemistry to create and optimize synthetic cell models with tunable properties.

Contribution

The novel use of dynamic covalent boronate chemistry enables in situ formation and optimization of cytomimetic microdroplets.

Findings

Dynamic zwitterionic polyboronates spontaneously form microdroplets when cationic and anionic catechols are added to polymeric boronic acid.

Material properties of membranized coacervate microdroplets can be modulated in situ without synthesizing new polymers.

The approach allows for adaptive cytomimetic optimization and potential application to diverse synthetic cell architectures.

Abstract

Bioinspired synthetic
cells are rapidly transforming the way we
interrogate the principles of cellular life and the development of
bioengineering and medical applications. However, despite significant
progress in modeling cell-like behavior, material engineering remains
a time-consuming and often behind-the-scenes endeavor when optimizing
cytomimetic functions. Here, we describe how dynamic covalent chemistry
can be used to bypass this bottleneck using membranized coacervate
microdroplets (MCM) as synthetic cell models. Specifically, the potential
of dynamic covalent boronate chemistry for the in situ formation, interfacial stabilization, and adaptive cytomimetic optimization
of MCM is presented. Simultaneous addition of cationic and anionic
catechols to a polymeric boronic acid (BA) generates dynamic zwitterionic
polyboronates that spontaneously phase separate into microdroplets,
which can then be interfacially stabilized as MCM with a BA-functionalized
block copolymer. The cytomimetic properties, membranization, internal
dynamics, and enzymatic activity within the MCM can be modulated in situ using dynamic covalent libraries to fine-tune material
properties (either by adjusting the charge ratio between oppositely
charged catechols, varying the catechol-to-BA ratio, or introducing
auxiliary catechol dopants) without the need to synthesize, isolate,
purify, and characterize new polymeric materials. Application of this
technology to other catechols, multivalent BA, and synthetic cell
architectures holds promise for optimizing diverse biomimetic functions
and providing programmable synthetic cells with emerging properties.

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