バイオフィジクス:構成要素供給の遅延が分子組立を促進(Biophysics: delayed supply of building blocks facilitates assembly)

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2025-11-26 ミュンヘン大学(LMU)

LMUミュンヘンの研究チームは、複合タンパク質などの生体分子が自己組織化する際、構成要素(ビルディングブロック)の供給が遅れるほど、むしろ効率的に正しい構造が組み上がるという意外な原理を発見した。理論モデルとシミュレーションを用いた研究により、ビルディングブロックが一度に大量供給されると誤った配置や「不良構造」が増え、組立が停滞しやすい一方、段階的・遅延的な供給では、部分構造が安定に形成され、最終的な複合体が正確かつ速く完成することが示された。この現象は、タンパク質複合体の形成だけでなく、ウイルス殻(カプシド)や人工ナノ構造の自己集合にも当てはまる可能性が高い。研究結果は、生体内で複雑な分子機械が高い精度で組み上がる仕組みの理解を深めるとともに、ナノ材料設計や自己組織化材料の製造プロセスを最適化する新たな指針となる。

<関連情報>

区画化されたシステムにおける遅延促進自己組織化 Delay-facilitated self-assembly in compartmentalized systems

Severin Angerpointner, Richard Swiderski, and Erwin Frey
Proceedings of the National Academy of Sciences  Published:November 25, 2025
DOI:https://doi.org/10.1073/pnas.2515123122

Significance

Understanding how spatial separation and particle exchange influence self-assembly is essential for biology and designing biomolecularfcoupled by particle exchange systems. We uncover a mechanism—delay-facilitated assembly—in which slow exchange between compartments with different reaction rates significantly enhances both final yield and speed of self-assembly. This effect emerges from a separation of timescales: Rapid reactions occur within one compartment, while slower exchange with a low-reactivity compartment enables cooperative dynamics. By adjusting compartment sizes and exchange rates, systems can be tuned to optimize assembly without modifying the local chemistry. These findings offer a robust strategy for improving synthetic self-assembling systems and suggest that biological systems may similarly exploit slow exchange processes to enhance the effectiveness and reliability of molecular assembly.

Abstract

Self-assembly processes in biological and synthetic biomolecular systems are often governed by the spatial separation of biochemical processes. While previous work has focused on optimizing self-assembly through fine-tuned reaction parameters or using phase-separated liquid compartments with fast particle exchange, the role of slow intercompartmental exchange remains poorly understood. Here, we demonstrate that slow particle exchange between reaction domains can enhance self-assembly efficiency through a cooperative mechanism: delay-facilitated assembly. Using a minimal model of irreversible self-assembly in two compartments with distinct reaction and exchange dynamics, we identify scenarios where slow particle exchange maximizes yield and minimizes assembly time for given suboptimal reaction dynamics, even under conditions where isolated compartments would fail to facilitate any self-assembly. The mechanism relies on a separation of timescales between intracompartmental reactions and intercompartmental exchange and is robust across a wide range of geometries, including spatially extended domains with diffusive transport. We demonstrate that this effect enables geometric control of self-assembly processes through compartment volumes and exchange rates, eliminating the need for fine-tuning local reaction rates. These results offer a conceptual framework for leveraging spatial separation in synthetic self-assembly design and suggest that biological systems may use slow particle exchange to improve assembly efficiency.

生物化学工学
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