Inverse Design of DNA-Programmable Protein Colloidal Crystals.

Authors

Zhenyu Han, Young Jun Kim, Chad A Mirkin

Published in

Journal of the American Chemical Society. Oct 21, 2025. Epub Oct 21, 2025.

Abstract

Protein crystals are a promising class of porous materials with applications in catalysis, encapsulation, and structural biology. However, the chemical complexity of proteins renders their crystallization a largely empirical process with variable success. In contrast, DNA-functionalized nanoparticles have been crystallized into ordered superlattices with predictable architectures using highly specific and tunable DNA-DNA interactions. Such programmability, however, has not yet been realized in protein crystals. Herein, we chemically modify protein oligomers with a DNA shell and crystallize the resulting protein-DNA conjugates using the principles of colloidal crystal engineering with DNA. When a new type of DNA design comprising three spacer-18 units and a 4-6 nucleotide sticky end was used, structures with greater crystallinity were produced (as compared to when traditional DNA designs used with inorganic assemblies were employed). Using an inverse design strategy, simple cubic, body-centered cubic (bcc), face-centered cubic (fcc), and cesium chloride (CsCl)-type lattices were synthesized by the judicious choice of DNA sequence and protein type. The resulting crystals exhibit Wulff morphologies, including those of fcc lattices, that were directly observable using optical microscopy; such morphologies are rarely achieved in the context of DNA-guided colloidal crystals and reflect the monodisperse protein building blocks. Furthermore, the annealing rate correlates with crystal growth, enabling the formation of crystals up to 80 μm in size. Given the structural, biological, and chemical diversity of natural and engineered proteins, DNA-directed protein colloidal crystallization is a powerful platform for generating a new class of programmable biomaterials with diverse structures and functionalities.

PMID:
41118555
Bibliographic data and abstract were imported from PubMed on 22 Oct 2025.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.