Controlling the Crystal Growth of DNA Molecules via Strategic Chemical Modifications

Intermolecular interactions are critical to the crystallization of biomolecules, yet the precise control of biomolecular crystal growth based on these interactions remains elusive. To understand the connections between the crystallization kinetics and the strength of intermolecular interactions, herein we have employed DNA triangular crystals and modified ones as a versatile tool to investigate how the strength of intermolecular interaction affects crystal growth. Interestingly, we have found that the 2'-O-methylation at sticky ends of the DNA triangle could strengthen its intermolecular interaction, resulting in the accelerated formation of smaller crystals. Conversely, phosphorothioate modification could weaken the sticky-end cohesion and delay the nucleation, resulting in formation of fewer but larger crystals. In addition, these modification effects were consistently observed in the crystallization of a DNA decamer. In one word, our experimental results demonstrate that the strength of intermolecular interaction directly impacts crystal growth. It suggests that 2'-O-methylation and phosphorothioate modification represents a rational strategy for controlling DNA molecules grow into desired crystals and it also facilitates structural determination.