Coiled-Coil Force-Sensing Peptides for In Vivo Signal Transduction
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Solution Overview
Problem
Current tools for detecting and quantifying mechanical forces in biological processes are large, disruptive, and difficult to use, relying on Forster Resonance Energy Transfer efficiencies that are tedious to perform and control, with no tools to detect mechanical signals and trigger biochemical responses.
Innovation Solution
Development of force sensing peptides comprising α-helix domains linked by a linker sequence, forming a coiled coil that changes conformation in response to forces above a threshold, with functional domains generating signals in the open conformation, linked to target molecules or substrates for detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional FRET-based tools are used to detect mechanical forces, then force detection capability is achieved, but the tools are large, disruptive, and difficult to use
Solution Approach 1:
The patent divides the force detection function into two separate components: a small force-sensing peptide that experiences the mechanical force and a separate fluorescent probe that detects the conformational change. This segmentation allows the force sensor itself to remain small and non-disruptive while the detection function is performed by a separate, easily manipulated probe molecule.
Solution Approach 2:
The patent introduces a fluorescent probe as an intermediary that binds to the force-sensing peptide. The probe acts as a mediator between the mechanical force (experienced by the peptide) and the detectable signal (fluorescence). This intermediary approach allows the force detection to be achieved without requiring the entire detection system to be large or complex.
2Measurement precision
If FRET-based tools are used to detect mechanical forces, then force detection is possible, but FRET efficiencies are difficult and tedious to perform and control
Solution Approach 1:
The patent replaces the complex FRET measurement system with a simpler fluorescence-based detection system. Instead of measuring energy transfer efficiencies that require precise control of multiple variables, the system uses direct fluorescence emission from the probe, which is easier to perform and control. The mechanical force detection is achieved through the conformational change of the peptide that affects probe binding or fluorescence properties.
3Measurement precision
If existing force detection tools are used, then mechanical signals can be detected, but no tools exist to detect mechanical signals and trigger biochemical responses
Solution Approach 1:
The patent designs the force-sensing peptide to serve multiple functions: it detects mechanical forces through conformational change, and the same conformational change can be coupled to various biochemical responses. The peptide structure is universal enough to work with different target molecules and can be operably linked to various functional domains for different biochemical outputs, making it versatile for various applications.
Solution Approach 2:
The patent creates a dynamic system where the peptide structure transitions from a closed conformation (no force) to an open conformation (force applied). This dynamic conformational change can be coupled to different biochemical responses, allowing the same force-sensing mechanism to trigger different downstream effects depending on what the peptide is linked to.
4Measurement precision
If coiled coil domain is used as force sensor, then force detection threshold can be set, but the peptide must undergo conformational change which may affect target molecule
Solution Approach 1:
The patent places the force-sensing peptide at a specific location within the target molecule or cellular structure where it can detect forces without interfering with critical functions. The peptide is designed to sense forces in a localized region while the rest of the target molecule maintains its normal structure and function. This localized sensing approach minimizes the impact of the conformational change on the overall target.
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 precise detection and quantification of mechanical forces in vivo, allowing for the use of these peptides in various biological processes, including cell division and adhesion, without disrupting cellular functions.
Implementation Method 1
the coiled coil domain undergoes a conformational change to an open conformation in the presence of a force above an uncoiling threshold level for the coiled coil domain
Data Source
AI summary
Force-sensing peptides that can be used as sensor molecules or can be used for signal transduction by detecting a force and translating the force into a biological signal are described as well as methods of using the force-sensing peptides.