Protein Binding Affinities Found to Differ Between 2D Materials

A group of researchers recently published a paper in The Journal of Physics Chemistry Letters that demonstrated the feasibility of using in-plane tin sulfide (SnS2) and molybdenum disulfide (MoS2) heterostructures for protein sequencing. 

Protein Binding Affinities Found to Differ Between 2D Materials

Study: Navigated Delivery of Peptide to the Nanopore Using In-Plane Heterostructures of MoS2 and SnS2 for Protein Sequencing. Image Credit: unoL/Shutterstock.com

Significance of Protein Sequencing

Proteins are considered critical components of life as they perform crucial functions in living cells to ensure cell viability and maintain the proper functioning of the body. The success of deoxyribonucleic acid (DNA) sequencing has encouraged researchers to sequence and sense proteins to obtain three-dimensional (3D) structure and high-resolution sequence information of a single protein molecule.

The information can help in comprehending the behavior and functions of protein over a certain duration, which are crucial for studying the pathogenic mechanisms and biological processes of protein at a single-molecule level.

Existing Protein Sequencing Methods and their Limitations

Existing protein sequencing methods, such as mass spectrometry (MS) and Edman degradation (ED), are ineffective for protein sequencing as they cannot measure single-molecule properties and require extremely purified samples. Other single-molecule techniques to sequence and detect proteins, such as fluorescence resonance energy transfer (FRET), also have limitations as they require narrow temporal bandwidth or site-specific labeling.

Although nanopore platforms were used effectively for DNA sequencing, using these platforms for protein sequencing can be challenging as, unlike DNA molecules, a protein molecule consists of over 20 amino acids with different hydrophobicities and charged states. To develop a nanopore sensor for accurate and fast protein sequencing, the protein must be manipulated in a controlled manner through the nanopore.

Importance of Nanomanipulation for Protein Sequencing

Nanomanipulation technology can eliminate the limitations of conventional driving methods and micromachine structure. Biological or small-molecule proteostasis regulators can be used to manipulate the location, conformation, and concentration of proteins. However, the integration of biological manipulators into a silicon-based chip is notably challenging.

Stacked two-dimensional (2D) materials and electro-osmosis used to manipulate and capture biomolecules in a solid-state nanopore are also ineffective for protein sequencing due to the possibility of nanopore clogging, which necessitates the identification of better ways to navigate protein molecules to the nanopore sequentially in proper order before the start of nanopore sensing.

Protein sequencing in liquid has gained a lot of attention owing to its potential in several fundamental applications. Although proteins can be detected in unfolded or folded conformations at the single amino acid level through a biological nanopore, sequencing peptides through a nanopore with limited entry events and samples remains a significant challenge as peptides cannot be kept inside the sensing area for an extended duration due to Brownian motion.

Rapid developments in material synthesis have allowed the combination of different materials to synthesize heterostructures. A capillary-force-driven rolling-up synthesis method can be utilized to fabricate an in-plane interconnected, vertically stacked, and high-quality synthetic heterostructure. These artificial heterostructures with atomically sharp and clean interfaces can help in manipulating individual protein molecules due to varying affinities between solid-state membranes and proteins.       

Novel Way of Protein Sequencing

In this study, researchers theoretically designed a versatile protein detection and manipulation chip using isomorphic 2D materials SnS2 and MoS2 to deliver the unfolded peptide to the nanopore sensing region in an ordered and controlled manner. 

SnS2 and MoS2 were selected to synthesize the heterostructure as they possess different intermolecular potentials in their surroundings, which can be used to alter the protein conformations. Initially, the binding affinities of these 2D materials to protein molecules were investigated by performing molecular dynamics (MD) simulations.

The simulations demonstrated a strong binding between the MoS2/SnS2 membrane and peptide. However, the electrostatic interaction energy between SnS2 or MoS2 membrane and peptide was extremely small/insignificant due to the lack of charge in the (FMWV)3FMW sequence of the peptide. Thus, the binding was attributed to the van der Waals (vdW) force owing to the vdW interaction energies between two closely located objects. The vdW interaction energy between SnS2 and peptide was significantly stronger compared to the energy between MoS2 and peptide, which confirmed that protein possesses a stronger binding affinity to the SnS2 membrane.

Based on the binding affinity results, researchers investigated the possibility of differentiating protein compositions precisely, navigating the peptide to the nanopore effectively along the SnS2 nanostripe, and energetically confining the peptides in nanostripes with different shapes through MD simulations. The traditional MD package Nanoscale Molecular Dynamics (NAMD2) with a 2fs time step and periodic boundary conditions in every direction was employed to perform all MD simulations.

Significance of the Study

The MoS2/SnS2/MoS2 heterostructure was designed successfully. The peptide spontaneously diffused from the MoS2 region to the SnS2 region, and by shrinking the SnS2 domain to a nanostripe with a width of a few nanometers, the peptide was constrained effectively in the nanostripe region. The well-navigated movement of the peptide was realized along different-shaped nanostripes by changing the applied electric field direction in real time. 

Protein samples in electrolyte were initially absorbed in the SnS2 stripe of the heterostructure, and then the peptide navigated to the nanopore, which prevented irregular entry events and nanopore clogging.

After the peptide was delivered successfully to the nanopore region, the peptide residues outside the nanopore were bound stably to the nanostripe, and no fluctuation was observed in them during translocation. The stable binding reduced the speed of the peptide translocation process and prevented ionic current fluctuations owing to the change in protein conformation.

Different ionic current blockades were observed by calculating the ionic current through the nanopore owing to the varying compositions of peptides, which confirmed the effectiveness of the designed heterostructure platform in differentiating and sensing proteins.

Moreover, the sensing accuracy of the platform can be improved by repeating the detection experiments and capturing a large number of protein samples in an orderly manner. Improving the sensing accuracy of the heterostructure is crucial to using the heterostructure for potential sequencing of proteins and is specifically effective for certain rare molecule samples that cannot be synthesized by simple molecular amplification or purification and extraction from living cells. 

To summarize, the findings of this study theoretically demonstrated that in-plane MoS2/SnS2/MoS2 heterostructures could be effective for protein sequencing. However, more research is required to investigate whether the platform can effectively differentiate up to 21 amino acids.

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Source

Sha, J., Wu, G., Shen, Y. et al. Navigated Delivery of Peptide to the Nanopore Using In-Plane Heterostructures of MoS2 and SnS2 for Protein Sequencing. The Journal of Physics Chemistry Letters 2022. https://doi.org/10.1021/acs.jpclett.2c00533

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Samudrapom Dam

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Samudrapom Dam

Samudrapom Dam is a freelance scientific and business writer based in Kolkata, India. He has been writing articles related to business and scientific topics for more than one and a half years. He has extensive experience in writing about advanced technologies, information technology, machinery, metals and metal products, clean technologies, finance and banking, automotive, household products, and the aerospace industry. He is passionate about the latest developments in advanced technologies, the ways these developments can be implemented in a real-world situation, and how these developments can positively impact common people.

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