Year: 2026
Type: preprint
Abstract: Three-dimensional protein crystals are ordered, porous macroscopic materials with potential applications in catalysis, biosensing, and biomedicine. However, most protein crystals are obtained by empirical screening, providing limited control over the lattice architecture, pore geometry or component composition that determine material function. Here, we present a modular strategy for the programmable design of highly porous, framework-like protein crystals using predefined protein-protein interactions. This strategy yielded over 30 distinct protein crystals, including single-component and multicomponent P 2 1 3 and I 2 1 3 lattices that grow to over 100 µm in size. Small-angle X-ray scattering and electron microscopy showed close agreement between experimental lattices and computational models. RFdiffusion-guided design generated isomorphous variants with matched lattice parameters, enabling coherent protein crystal alloys, epitaxial core–shell growth and reversible shell assembly. The designed crystals exhibit tunable mesoporous architectures, with limiting apertures of 2–18 nm, and support genetically encoded incorporation of fluorescent protein guests. These results establish a general route to programmable lattice engineering of protein crystals and position them as genetically encoded, compositionally tunable mesoporous materials.
Authors: Zhe Li, Shunzhi Wang, Will Sheffler, Yang Hsia, Byeongdu Lee, Greg L. Hura, Muammer Y. Yaman, Bo Liu, Ryan D. Kibler, Neville P. Bethel, David Chmielewski, Danny D. Sahtoe, Wei Yang, Hao Shen, Hanlun Jiang, Una Nattermann, Yunbing Shui, Haoheng Liu, Hannah Nguyen, Alex Kang, Justin Decarreau, Andrew J. Borst, Asim K. Bera, Banumathi Sankaran, David S. Ginger, David Baker
Institutions: University of Washington, Southern University of Science and Technology, NYU Langone Health, Argonne National Laboratory, Advanced Photon Source, Lawrence Berkeley National Laboratory, University of California San Diego, Hubrecht Institute for Developmental Biology and Stem Cell Research, Shenzhen Medical Academy of Research and Translation, University of California, Berkeley, Howard Hughes Medical Institute
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Funders: U.S. Department of Energy, University of Washington, National Natural Science Foundation of China, Southern University of Science and Technology, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, Office of Research Infrastructure Programs, National Institutes of Health, Argonne National Laboratory, Lawrence Berkeley National Laboratory
Awards: G102163711, G107546177, G1079818582, G1143651532, G1286236842, G1313983767, G1386414003, G1420670123, G1664757510, G1767990418, G1910259592, G2287611682, G2539837713, G262962599, G2638771445, G2849897711, G3075337988, G3083819904, G3257500209, G334911014, G382641700, G3924411600, G409777406, G4155925329, G4158950854, G419881185, G42916606, G4429385918, G4501827968, G4686945193, G498139845, G5607048534, G6188209572, G6206027980, G6652958823, G6848031779, G6918803902, G704498496, G7354628648, G78868261, G7912248388, G8229677252, G8682639235, G880751848, ALS Efficiently Networking Advanced Beam Line Experiments (ALS-ENABLE), NE-CAT: A Resource for Advanced Macromolecular Crystallography, G969889393, G993149817
OpenAlex ID: W7204267325