Molecular Engineering of DNA Condensates: Harnessing Phase Transitions for Precise Control of Catalytic Functions

Precise manipulation of macromolecular condensates is a pivotal tool for dissecting cellular mechanisms and engineering advanced biomaterials. This study presents a DNA molecular engineering approach that enables dynamic and reversible regulation of phase transitions in DNA condensates. The results show a strong association between the degree of phase transition and the functional properties of DNA condensates, driven by significant alterations in their internal physical microenvironment. Factors such as internal viscosity, fluidity, and the ability to incorporate small molecules into biomolecular condensates are shown to play critical roles in these transitions. This work provides a compelling example of dynamic programming of biomolecular condensate phase transitions, while also offering deeper insights into the interplay between their physical microenvironment and biological functions. These findings support to a broader understanding of the principles underlying biomolecular phase transitions in living systems, with implications for cellular processes, disease mechanisms, and biomedical applications.