DOE OSTI · 3377136
Programmed synthesis of mesoporous protein crystals in cellular reactors
Abstract
Protein crystals are naturally derived mesoporous materials with versatile structures and physicochemical properties. Here we introduce an intracellular synthesis platform that enables controllable and programmable protein crystallization. In live cells, we show that, after initial nucleation, steady protein expression governs crystal growth, yielding predictable, tunable dynamics in live cells. Exploiting this feature, we combined HaloTag and click chemistries to achieve modular, programmable immobilization of diverse guest materials with spatial patterning down to ~100 nm resolution. We further demonstrated the sequential release of immobilized materials in physiologically relevant fluids. As a proof of concept, we programmed particles to carry human fibroblast growth factors in distinct layers, which elicited designed oscillatory Akt signalling patterns in cell culture. Finally, this work outlines a programmable method for producing mesoporous materials, with possible applications in catalysis and biomedicine.
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Yang, Hongru [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0009000612128505), Lin, Dian-Zhao [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0000000311772308), Li, Zhe [Univ. of Washington, Seattle, WA (United States); Southern University of Science and Technology, Shenzhen (China)] (ORCID:0000000194024940), Yan, Yuqing [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0009000819564689), Zhao, Zuo-Han [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0000000318126237), Lee, Byeongdu [Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)] (ORCID:0000000325148805), Song, Chang Woo [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0000000235963291), Wang, Shunzhi [Univ. of Washington, Seattle, WA (United States)] (ORCID:0000000150337478), Lu, Jiaxi [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0009000685021952), Wang, Yimei [Johns Hopkins Univ., Baltimore, MD (United States)], Sun, Yongzhi [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0000000152676780), Livi, Ken [Johns Hopkins Univ., Baltimore, MD (United States)], Baker, David [Univ. of Washington, Seattle, WA (United States)] (ORCID:0000000178966217), Liu, Yayuan [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0000000207184784), Lin, Dingchang [Johns Hopkins Univ., Baltimore, MD (United States)] (ORCID:0000000293545952). 2026-06-15. Programmed synthesis of mesoporous protein crystals in cellular reactors. https://doi.org/10.1038/s41565-026-02198-x
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