Encoding hierarchical assembly pathways of proteins with DNA.

Area of Science:

• Materials Science
• Biotechnology
• Synthetic Biology

Background:

• Natural materials exhibit complex structures through hierarchical assembly.
• Synthetic materials struggle to replicate this complexity due to challenges in controlling building block interactions.

Purpose of the Study:

• To develop a method for programmable hierarchical assembly of protein-DNA materials.
• To exploit protein chemical anisotropy and DNA ligand programmability for controlled assembly.

Main Methods:

• Designed DNA ligands with varying interaction strengths (strong and weak) on a model protein (Sp1).
• Utilized spatial encoding of DNA ligands to direct assembly pathways.
• Engineered sequential assembly stages driven by differential DNA-DNA interaction strengths.

Main Results:

• Achieved highly directional assembly using strong DNA interactions.
• Demonstrated emergent second-stage assembly through multivalency from initial weak interactions.
• Showed that DNA design can dictate distinct structural outcomes from a single assembly pathway.

Conclusions:

• Developed a strategy for programming multistep hierarchical assembly of protein-DNA materials.
• Enabled the creation of diverse protein-DNA materials through precise control over building block interactions.
• Established a framework for encoding structural and chemical information into building blocks for designed assembly.