Connecting rare DNA conformations and surface dynamics using single-molecule resonance energy transfer

Area of Science:

• Nanotechnology
• Biophysics
• Materials Science

Background:

• Advancing DNA-directed self-assembled nanomaterials requires understanding single-stranded DNA (ssDNA) behavior at interfaces.
• Interfacial dynamics and molecular conformation are critical factors in nanomaterial assembly.

Purpose of the Study:

• To investigate the mechanistic understanding of ssDNA behavior near amine-modified surfaces.
• To correlate ssDNA molecular conformation with interfacial dynamics, including desorption and surface mobility.

Main Methods:

• Utilized total internal reflection fluorescence microscopy (TIRFm) for single-molecule resonance energy transfer (smRET) measurements.
• Observed over 10^5 ssDNA trajectories to analyze dynamic behavior and conformational states.
• Employed lattice simulations of adsorbed self-avoiding polymers for comparative analysis.

Main Results:

• Identified two ssDNA populations: a common coiled state and a rare (<5%) weakly bound conformation.
• The coiled state showed slow diffusion and decreasing fluctuations with increasing end-to-end distance, matching simulations.
• The weakly bound state exhibited faster diffusion and higher conformational fluctuations, correlating with desorption events.

Conclusions:

• A weakly bound ssDNA conformation significantly influences surface association and dynamics.
• This conformation's role in DNA hybridization and its dependence on solution/surface conditions are crucial for optimizing self-assembled nanomaterials.
• Further research into favoring this conformation could enhance DNA-based nanomaterial design.