Trends Biotechnol. 2026 Sep 29:S0167-7799(26)00378-1. doi: 10.1016/j.tibtech.2026.09.008. Online ahead of print.

ABSTRACT

Control over the morphology and function of self-assembling polymers remains a central challenge in engineering adaptive biomaterials and synthetic biological systems. Here, we establish that recombinant elastin-like polypeptide-resilin-like polypeptide diblocks can be programmed through incorporation of unnatural amino acids (uAAs) to undergo multistep, temperature-dependent phase transitions that generate shape-shifting nanostructures, including micelles, vesicles, and higher-order assemblies not typically accessible in conventional protein materials, thereby expanding their structural and functional design space. Incorporation of only six uAAs (<1.5% of residues) is sufficient to program phase behavior and assembly pathways, with uAA hydrophobicity and sequence position governing morphology and structural transitions. Photo-switchable uAAs further enable reversible, light-driven control over nanostructure morphology, modulating substrate encapsulation and enzymatic activity. Together, these findings define a genetically encoded design framework for adaptive protein materials and expand opportunities for their use in biotechnology, including synthetic organelle-like systems, dynamic biomolecular assemblies, responsive biocatalysis, and drug delivery.

PMID:42810892 | DOI:10.1016/j.tibtech.2026.09.008