DNA-Encoded Hierarchical Protein Assembly via Patch Hybridization
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Solution Overview
Problem
Current methods struggle to control and program multi-step assembly pathways of nanoscale building blocks, limiting the ability to design hierarchical structures with specific properties and functions, due to challenges in defining interaction locations and types on synthetic building blocks.
Innovation Solution
The method involves spatially encoding programmable interacting ligands (DNA) onto the surface of chemically addressable proteins, using mutagenesis to define chemical anisotropy and introduce orthogonal DNA interactions, allowing for directional assembly and multi-step hierarchical assembly pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If synthetic nanoscale building blocks are used for hierarchical assembly, then the ability to control bottom-up assembly is improved, but the ability to program through hierarchical mechanisms remains limited due to difficulties in defining interaction locations and types
Solution Approach 1:
The building block surface is segmented into distinct patches (e.g., patch A, patch B) with specific DNA ligands at defined locations. This segmentation allows independent control of multiple interaction sites, enabling complex hierarchical assembly pathways while maintaining ease of operation through modular design
Solution Approach 2:
DNA ligands serve as intermediary elements that mediate interactions between protein building blocks. The DNA-mediated recognition provides programmable specificity and control over hierarchical assembly pathways, resolving the contradiction between operational ease and programming capability
2Adaptability or versatility
If multiple DNA ligands are defined on building block surfaces, then hierarchical assembly pathways can be programmed, but the complexity of defining number, type, and location of interactions increases
Solution Approach 1:
Different patches on the building block surface are assigned different DNA ligand types and sequences (local quality variations). This allows each patch to participate in specific interactions required for particular assembly pathways, providing adaptability without requiring global redesign of the entire building block
Solution Approach 2:
The DNA ligands are pre-defined and conjugated to specific locations on the building block surface before assembly occurs. This preliminary action establishes the interaction map in advance, enabling programmable hierarchical pathways while simplifying the actual assembly process
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables the controlled synthesis of novel, hierarchically structured materials by programming the assembly pathways, mimicking natural processes and achieving specific structural outcomes.
Implementation Method 1
the one or more polynucleotides of the patch A hybridizes to the one or more polynucleotides of the patch A'
Implementation Method 2
the one or more polynucleotides of the patch B hybridizes to the one or more polynucleotides of the patch B'
Data Source
AI summary
Provided herein are hierarchical protein structures comprising two or more proteins extending in one or more dimensions, the hierarchical protein structure comprising: a first protein comprising: (i) a patch A comprising one or more polynucleotides conjugated to the surface of the first protein; and (ii) a patch B comprising one or more polynucleotides conjugated to the surface of the first protein; and a second protein comprising: (i) a patch A′ comprising one or more polynucleotides conjugated to the surface of the second protein; and (ii) a patch B′ comprising one or more polynucleotides conjugated to the surface of the second protein; wherein the one or more polynucleotides of the patch A hybridizes to the one or more polynucleotides of the patch A′, and/or the one or more polynucleotides of the patch B hybridizes to the one or more polynucleotides of the patch B′ to form the hierarchical protein structure. Also provided are methods of making the hierarchical protein structures.