Oligomerized Protein-Polymer Conjugates for Biosensor Sensitivity
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Solution Overview
Problem
Current protein-polymer conjugates with small protein blocks exhibit weak ordering, limiting the sensitivity of biosensors due to the entropic penalty at interfaces and the need for higher molecular weight protein blocks to achieve well-ordered structures.
Innovation Solution
Increasing the molecular weight of low molecular weight protein blocks by oligomerizing engineered binding proteins, such as rcSso7d.SA, and conjugating them with PNIPAM, results in well-ordered lamellar structures and enhanced biosensing capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If small protein blocks are used in protein-polymer conjugates, then the ease of manufacture and recombinant expression are improved, but the nanoscale ordering and biosensor sensitivity deteriorate due to weak ordering and entropic penalty at interfaces
Solution Approach 1:
The patent divides the protein block into oligomeric units (dimers, trimers, tetramers) of small proteins like Sso7d, rather than using a single large protein block. This segmentation allows the system to maintain the ease of expressing small proteins while achieving higher molecular weight and better ordering through self-assembly of multiple oligomeric units into well-ordered lamellar structures
Solution Approach 2:
The patent creates composite protein-polymer conjugates where oligomeric protein blocks are conjugated to polymer blocks (such as PNIPAM). This composite structure combines the advantages of small proteins (ease of expression) with the ordering capabilities of block copolymers, enabling well-ordered nanoscale structures that enhance biosensor performance
2Manufacturing precision
If higher molecular weight protein blocks are used to achieve well-ordered structures, then the nanoscale ordering and biosensor sensitivity are improved, but the complexity of protein engineering and expression increases
Solution Approach 1:
Instead of engineering single large protein blocks, the patent segments the protein component into oligomeric assemblies of small, easily expressed proteins. This approach achieves the necessary molecular weight for ordering while avoiding the complexity of expressing and engineering large, complex proteins
Solution Approach 2:
The patent utilizes the self-assembly capability of oligomeric protein blocks to spontaneously form well-ordered structures. The system self-organizes into lamellar phases without requiring complex external engineering or assembly protocols, reducing the overall complexity of the system
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
The oligomerization of protein blocks in protein-polymer conjugates leads to a significant reduction in the limit of detection, with trimer conjugates providing a 3-fold reduction compared to monolayers, and improved nanoscale ordering, enhancing the sensitivity and functionality of biosensors.
Implementation Method 1
it has been demonstrated that these conjugates assemble into ordered nanostructures similar to coil-coil diblock copolymers
Implementation Method 2
the self-assembly of protein-polymer conjugates exhibits notable differences from that of traditional block copolymers... highly asymmetric phase behavior... re-entrant order-disorder transition (ODT) behavior
Data Source
AI summary
The present disclosure relates to protein-polymer conjugates comprising an engineered binding oligomer protein and a polymer for detection of a ligand of interest, methods, compositions and kits thereof.