Beta-Sheet Nanofibers for Modular Protein Integration

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Solution Overview

Problem

Current approaches fail to achieve modular and tunable control over integrated protein ligand composition in supramolecular assemblies, particularly in creating β-sheet nanofibers with multiple biologically active proteins at precise concentrations, limiting design flexibility and functional properties for biomedical applications.

Innovation Solution

A nanofiber composition comprising a β-sheet nanofiber structure formed by a combination of peptide A and peptide B, where peptide A can transition from a non-β-sheet structure to a β-sheet structure, allowing for precise control of molar ratios and integration with various compounds to create heterogeneous structures with unique biological properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current approaches are used to create supramolecular assemblies, then assembly formation is achieved, but modular and tunable control over integrated protein ligand composition is not achieved

Engineering Contradiction:

Improvemodular and tunable control over protein ligand compositionVSAvoidprecise concentrations of multiple biologically active proteins

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The invention divides the assembly system into distinct components: a scaffold protein that forms the supramolecular structure and separate bioactive protein ligands that can be independently controlled. This segmentation allows each component to be optimized and controlled separately, enabling precise compositional control of multiple proteins in the final assembly

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention uses parameter changes in the form of adjustable stoichiometric ratios during the assembly process. By controlling the relative concentrations and addition sequences of different protein components, the system achieves tunable composition of integrated protein ligands while maintaining stable assembly formation

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If supramolecular assemblies with multiple different folded protein ligands at precise concentrations are created, then design flexibility and functional properties are improved, but existing approaches cannot achieve this compositionality

Engineering Contradiction:

Improvedesign flexibility for biomaterialsVSAvoidcomplexity of achieving multi-protein composition control

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The scaffold protein serves multiple functions: it provides the structural framework for assembly formation, acts as a platform for integrating multiple different protein ligands, and enables compositional control through its interaction properties. This multi-functionality simplifies the overall system design while achieving complex multi-protein compositions

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention creates composite supramolecular assemblies by combining the scaffold protein with multiple different bioactive protein ligands. This composite approach allows each protein component to contribute its unique functional properties while maintaining precise compositional control through the defined assembly stoichiometry

Inventive Principle:

Principle #40Composite materials

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

Enables the formation of nanofibers with tunable composition and bioactive properties, suitable for applications in immunotherapy, cell culture, and tissue engineering, by allowing for the precise integration of bioactive proteins and antigens, enhancing immune responses and cellular functions.

Implementation Method 1

Polypeptides that non-covalently assemble into supramolecular structures, such as nanofibers and nanoparticles

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

the peptide A may be non-β-sheet peptide tags... The non-β-sheet peptide may refer to a peptide that forms a structure other than a β-sheet structure when expressed or isolated... However, the non-β-sheet peptide tags may form a β-sheet structure in the presence of a β-sheet peptide

Methodology Applied

Scientific Effectβ-sheet structure formation: Crystallisation

Data Source

PatentUS9200082B2Methods and compositions involving fibrillizing polypeptides for nanofibers

Publication Date: 2015.12.01 UNIVERSITY OF CHICAGO

AI summary

Embodiments of the invention are directed to fibrillar adjuvants. For example, epitopes assembled by a synthetic peptide domain into nanofibers comprising a β-fibrillization peptide may elicit high antibody titers in the absence of any adjuvant. In certain embodiments, multiple different antigens may be integrated into polypeptide nanofibers, providing biomaterials with modular and precise composition of bioactive proteins.