The design and scalable synthesis of robust 2D biological ultrathin films with a tunable structure and function and the ability to be easily transferred to a virtually arbitrary substrate remain key challenges in chemistry and materials science. Here, we implicate the potential of the thiol-disulfide exchange reaction in the synthesis of a macroscopic 2D ultrathin proteinaceous film with the potential for scaled-up fabrication and on-demand encapsulation/release of functional molecules. The synthesis success is determined by the chemoselectivity and site-specificity of the reaction between the Cys6-Cys127 disulfide bond of native lysozyme and cysteine, as supported by the superior redox potential of the Cys6-Cys127 disulfide bond over that of other disulfide bonds in native lysozyme and other unreactive proteins. The partially unfolded lysozyme-cysteine conjugate monomers are formed by this strategy, which then further aggregate at the air/water or solid/liquid interface to form an ultralarge 2D nanofilm (e.g., 900 cm2) with ~100% optical transparency. On the basis of amyloid-like aggregation inside the nanofilm, this material presents robust adhesion onto a virtually arbitrary substrate and on-demand controllability to mediate the encapsulation and release of small, mid-sized and large molecules without significant activity loss upon the surface immobilization of active proteins. Our approach provides an important application for the thiol-disulfide exchange reaction in the biocompatible large-scale preparation of 2D proteinaceous nanofilms and coatings with the capability of tunable functional molecular block encapsulation and release.

Yan Xu, Yongchun Liu, Xinyi Hu, Rongrong Qin, Hao Su, Juling Li, Peng Yang*, Synthesis of 2D Ultralarge Protein Supramolecular Nanofilm by Chemoselective Thiol-Disulfide Exchange and Emergent Functions. Angew. Chem. Int. Ed. DOI: 10.1002/anie.201912848 and 10.1002/ange.201912848, Just Accepted.