Oligolysine Enhances and Inhibits DNA Condensate Formation

H Ohno and J Kijima and Y Ochi and M Shoji and J Taira and T Mabuchi and Y Sato, ACS OMEGA, 10, 15781-15789 (2025).

DOI: 10.1021/acsomega.5c01928

The formation of biomolecular condensates via phase separation relates to various cellular functions. Reconstituting these condensates with designed molecules facilitates the exploration of their mechanisms and potential applications. Sequence-designed DNA nanostructures enable the investigation of how structural design influences condensate formation and the construction of functional artificial condensates. Despite the high designability of DNA-based condensates, free nanostructures that do not assemble into condensates remain a challenge. Combining DNA nanostructures with other molecules, such as peptides, represents a promising approach to overcoming the limitations of DNA condensates and gaining a deeper understanding of molecular condensates. Herein, we report the effects of cationic oligolysines with several residues on DNA condensate formation assembled from Y-shaped DNA nanostructures. DNA condensate formation was enhanced by oligolysines at an appropriate L/P ratio, which refers to the ratio of positively charged amine groups in lysine (L) to negatively charged nucleic acid phosphate groups (P). Oligolysines with five residues enhanced condensate formation while maintaining the sequence-specific interaction of DNA. In contrast, oligolysines inhibited condensate formation depending on the L/P ratio and residue number. This was attributed to nanostructure deformation caused by oligolysines. These results suggest that the amount and length of cationic peptides significantly affect the self-assembly of branched DNA nanostructures. This study offers important insights into biomolecular condensates that can guide further development of DNA/peptide hybrid condensates to enhance the functions of artificial condensates for use in artificial cells and molecular robots.

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