Synthetic FG-Repeat Hydrogels for Selective Macromolecule Filtering

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current synthetic polymer hydrogels lack the selective filtering capability and efficiency of natural nucleoporin hydrogels, which are crucial for controlling the transport of macromolecules across the nuclear envelope, due to complex protein sequences and low recombinant yields.

Innovation Solution

Artificially engineered protein polymers, such as P-1NLP, P-2NLP, and P-cNspI-P, are designed to replicate the selective transport properties of nucleoporin hydrogels using consensus repeats from well-investigated nucleoporins, allowing for the creation of synthetic hydrogels with tunable selectivity and transport rates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If natural nucleoporin sequences are used to create hydrogels, then selective filtering capability is achieved, but manufacturing complexity and low recombinant yields occur

Engineering Contradiction:

Improveselective filtering capabilityVSAvoidrecombinant yield

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent creates simplified copy versions of natural nucleoporin sequences (consensus repeats) that replicate the essential selective filtering function. These consensus repeats are derived from analyzing multiple natural nucleoporin sequences and creating a simplified model that captures the core functionality without the complexity of natural sequences, thereby improving manufacturability while maintaining selective transport capability

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent modifies the natural nucleoporin sequences by changing parameters such as repeat number, sequence composition, and structural organization. By optimizing these parameters in the consensus repeat design, the patent achieves both improved recombinant expression yields and retained selective filtering functionality, resolving the contradiction between manufacturing ease and functional reliability

Inventive Principle:

Principle #35Parameter changes

2Reliability

If complex natural protein sequences are used, then selective transport function is achieved, but device complexity and manufacturing difficulty increase

Engineering Contradiction:

Improveselective transport functionVSAvoidprotein sequence complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the complex natural nucleoporin sequences into repeating modular units (consensus repeats). Each repeat contains the essential functional elements for selective transport, and multiple repeats are arranged in a standardized pattern. This segmentation simplifies the overall sequence complexity while preserving the selective transport function through modular design

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses homogeneous consensus repeat sequences that are identical or highly similar throughout the hydrogel structure. This homogeneity simplifies manufacturing and characterization compared to heterogeneous natural sequences, while the repeated pattern maintains the collective functionality needed for selective transport. The uniform structure allows for easier recombinant production and quality control

Inventive Principle:

Principle #33Homogeneity

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

These synthetic hydrogels exhibit selective filtering capabilities, enabling the sequestration of macromolecules and serving as models for nuclear permeability assays, while providing a tool for material engineering and drug delivery applications.

Implementation Method 1

These segments of FG-nucleoporins form a mass of chains which allow smaller molecules to diffuse through but exclude large hydrophilic macromolecules

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 2

Ran is small enough that it can diffuse through nuclear pores down its concentration gradient without interacting with nucleoporins

Methodology Applied

Scientific EffectConcentration gradient diffusion: Diffusion

Implementation Method 3

These synthetic hydrogels exhibit selective filtering capabilities, enabling the sequestration of macromolecules

Methodology Applied

Scientific EffectSelective filtering: Filter (physical)

Data Source

PatentUS10220098B2Artificially engineered protein hydrogels to mimic nucleoporin selective gating

Publication Date: 2019.03.05 MASSACHUSETTS INST OF TECH

AI summary

Disclosed are synthetic polypeptides modeled after NspI nucleoporin which are useful for forming hydrogels characterized by selective permeability. The polypeptides and hydrogels formed from them include phenylalanine-glycine (FG) repeats, which are believed to participate in the selectivity of the nuclear pore complex. Also disclosed are filtering devices, drug delivery devices, and methods of separating or selectively filtering macromolecules using the hydrogels.