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

Phase-separated biomolecular condensates serve as functional elements of biological cells, as contributors to the formation of protocells in prebiotic systems during early life, and as a distinct form of material with a range of applications. Regulation of condensate mechanochemistry is of critical importance for their functions and properties. Photochemical processes, such as UV-induced chemical changes, are commonly observed in nature and can have both detrimental and constructive impacts on life, and are also readily implemented in engineering applications. However, how phase-separated condensate formation influences photochemical processes, and conversely, how photochemical reactions impact condensate dynamics, remains an open question. Combining scanning probe microscopy with optical imaging and control, we developed a first-of-its-kind assay that enables the study of mechanical transitions and fusion dynamics in condensate droplets, revealing that UV-induced thymine dimerization alters condensate nucleation and coalescence. Depending on the exposure and topological arrangement of thymine dimers, UV can induce a transition from liquid-like to solid-like behaviours or lead to aggregate formation. UV treatment also leads to compartmentalization in condensate systems by e.g., promoting the formation of arrested fusion droplets, which are stable against environmental changes. UV illumination can thus be leveraged to program the architecture and material properties of DNA-based biomolecular condensates, with implications for genome biology, the emergence of life on Earth, and engineering applications.