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<p>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. This work outlines a programmable method for producing mesoporous materials, with possible applications in catalysis and biomedicine.</p>

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Programmed synthesis of mesoporous protein crystals in cellular reactors

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • Hongru Yang,
  • Dian-Zhao Lin,
  • Zhe Li,
  • Yuqing Yan,
  • Zuo-Han Zhao,
  • Byeongdu Lee,
  • Chang Woo Song,
  • Shunzhi Wang,
  • Jiaxi Lu,
  • Yimei Wang,
  • Yongzhi Sun,
  • Ken Livi,
  • David Baker,
  • Yayuan Liu,
  • Dingchang Lin

摘要

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. This work outlines a programmable method for producing mesoporous materials, with possible applications in catalysis and biomedicine.