Multivalent Polymer Self-Assembly for Protein Nanostructure Stability

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Solution Overview

Problem

Conventional protein detection methods face challenges such as protein deformation, inefficient binding, and difficulty in maintaining protein activity and quantitative control on solid substrates, especially in producing three-dimensional protein nanostructures under specific conditions.

Innovation Solution

A multivalent polymer incorporating a multimerization peptide domain, derived from hagfish VLRB protein, is developed to form nano particles through self-assembly, enabling the creation of globular-shaped multimers with varying sizes, which can be used for sensitive protein detection and diagnostic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If proteins are adhered on a substrate surface by simple adsorption, then the immobilization process is simple and fast, but the protein structure is easily deformed and binding efficiency is reduced

Engineering Contradiction:
Improveimmobilization process simplicityVSAvoidprotein binding efficiency
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The invention uses a composite structure consisting of a core particle (providing structural stability) and a protein layer (providing binding function). This composite approach allows the protein to be immobilized in a stable, functional configuration rather than through simple adsorption, resolving the contradiction between ease of manufacture and binding efficiency.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The core particle is prepared in advance with specific surface properties that enable controlled protein attachment. This preliminary preparation of the support structure allows for optimized protein immobilization that maintains protein structure and function, rather than relying on random adsorption.

Inventive Principle:
Principle #10Preliminary action

2Stability of the object's composition

If proteins are immobilized on a substrate surface, then the protein probe can be fixed in position, but the protein may be washed out under intensive washing conditions or transferred to other molecules

Engineering Contradiction:
Improveprotein position stabilityVSAvoidprotein probe retention
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The protein is nested within or on the surface of a core particle structure, creating a hierarchical arrangement where the protein probe is protected by the core particle. This nested configuration provides both positional stability and protection against washing out or transfer to other molecules.

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The composite structure of core particle plus protein layer creates a stable immobilization system where the protein benefits from the structural support and protective environment of the core, preventing protein loss under intensive washing conditions.

Inventive Principle:
Principle #40Composite materials

3Productivity

If conventional methods are used to produce three-dimensional protein nanostructures, then the production process can be established, but special chemical treatment is necessary and the process time is relatively long

Engineering Contradiction:
Improvenanostructure production capabilityVSAvoidproduction process time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The core particle system enables self-assembly or self-organization of protein structures. The core particle's surface properties automatically guide protein arrangement into stable configurations, eliminating the need for complex chemical treatments and reducing production time while maintaining nanostructure formation capability.

Inventive Principle:
Principle #25Self-service

4Ease of operation

If protein probes are immobilized on a substrate surface, then the detection system can be constructed, but it is difficult to quantitatively control the protein probe immobilization and maintain the probe in active state

Engineering Contradiction:
Improvedetection system constructionVSAvoidprotein probe quantitative control
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The core particle is pre-prepared with controlled surface characteristics that enable predictable and quantitative protein attachment. This preliminary structuring of the support medium allows for precise control over the amount and state of immobilized protein probes, facilitating both easy system construction and quantitative control.

Inventive Principle:
Principle #10Preliminary action

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 multivalent polymer achieves stable and specific protein binding, maintaining high activity and sensitivity, allowing for the development of advanced protein nano chips and diagnostic kits with improved protein detection capabilities.

Implementation Method 1

monomers of hagfish VLRB protein aggregate to each other to form a multimer with a size of about 1,700 to 650 kDa, and the inventors recognized that this phenomenon is based on formation of a core by the hydrophobic tail (hydrophobic clustering, HC) at the carboxy terminal of VLRB protein

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

formation of a core by the hydrophobic tail (hydrophobic clustering, HC) at the carboxy terminal of VLRB protein to yield an antibody with globular-shaped multimer structure

Methodology Applied
Scientific EffectHydrophobic clustering: Hydrophobe

Data Source

PatentUS12037373B2Multimeric and multivalent polymer comprising multimerization peptide domain
Publication Date: 2024.07.16 EARWYNTECH
  • US12037373B2 patent drawing
  • US12037373B2 patent drawing
  • US12037373B2 patent drawing

AI summary

A multivalent polymer includes a multimerization peptide domain and a target protein fused directly or indirectly with the multimerization peptide domain. The multivalent polymer exhibits a probe effect by establishing a nano-size by self-assembly, and, accordingly, the multivalent polymer can be advantageously used in the development of a highly sensitive protein nano chip and the development of a diagnostic kit.