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.
Gonzalez et al. (2026) studied this question.