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<p>Phase-separated biomolecular condensates are functional elements in cells, contribute to protocell formation in prebiotic systems, and represent a distinct class of soft matter. Controlling condensate mechanochemistry is critical for function and material properties. Although photochemical processes are widespread in nature and can be harnessed in engineering, it remains unclear how condensate formation affects photochemistry, and conversely how photochemistry alters condensate dynamics. Using scanning probe microscopy combined with UV-controlled photochemistry and optical imaging, we develop assays to probe mechanical transitions and fusion dynamics in condensate droplets, revealing that UV-induced thymine dimerization alters condensate nucleation and coalescence. Depending on the frequency and topological arrangement of thymine dimers, particularly the balance between inter- and intrachain crosslinks, UV can drive transitions from liquid-like to solid-like states or induce aggregates. UV also promotes arrested fusion and stable compartmentalization of droplets, resilient to environmental changes and with implications for prebiotic chemistry and bio-inspired engineering.</p>

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Optically driven control of mechanochemistry and fusion dynamics of biomolecular condensates via thymine dimerization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月26日

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  • Vahid Sheikhhassani,
  • Faith H. K. Wong,
  • Daniel Bonn,
  • Jeremy D. Schmit,
  • Alireza Mashaghi

摘要

Phase-separated biomolecular condensates are functional elements in cells, contribute to protocell formation in prebiotic systems, and represent a distinct class of soft matter. Controlling condensate mechanochemistry is critical for function and material properties. Although photochemical processes are widespread in nature and can be harnessed in engineering, it remains unclear how condensate formation affects photochemistry, and conversely how photochemistry alters condensate dynamics. Using scanning probe microscopy combined with UV-controlled photochemistry and optical imaging, we develop assays to probe mechanical transitions and fusion dynamics in condensate droplets, revealing that UV-induced thymine dimerization alters condensate nucleation and coalescence. Depending on the frequency and topological arrangement of thymine dimers, particularly the balance between inter- and intrachain crosslinks, UV can drive transitions from liquid-like to solid-like states or induce aggregates. UV also promotes arrested fusion and stable compartmentalization of droplets, resilient to environmental changes and with implications for prebiotic chemistry and bio-inspired engineering.