Protein-Targeted Corona Phase Molecular Recognition

Technology #18316

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 Illustration of the possible fibrinogen—SWCNT interaction. The fibrinogen surface is coloured according to the hydrophobicity of each amino acid ranging from white (hydrophilic) to red (hydrophobic).The structure of the phospholipid-PEG constructs used in this study to suspend the SWCNT. (i) DPPEPEG(5000), (ii) DMPE-PEG(5000), (iii) DSPE-PEG(5000), (iv) DSPE-PEG(2000), (v) DSPE-PEG(2000)-Cyanur, (vi) DSPE-PEG(2000)-carboxylic acid (CA), (vii) DSPE-PEG(2000)-Maleimide, (viii) DSPE-PEG(2000)-[3-(2-Pyridyldithio)-propionyl] (PDP), (ix) DSPE-PEG(2000)-Amine, (x) DSPEPEG(2000)-Biotin, (xi) DSPE-PEG(350). The number in parentheses is the molecular weight of the PEG chain in DaltonsThe solvatochromic shift as a function of the SWCNT diameter to the power of negative 4 (d-4, blue dots) and its linear fit (solid red curve), and the fluorescent emission intensity for each wrapping (dashed black curve).The relative surface coverage of the polymer wrappings ranked in descending order.
Categories
Inventors
Professor Michael Strano
Department of Chemical Engineering, MIT
External Link (srg.mit.edu)
Gili Bisker
Department of Chemical Engineering, MIT
Managed By
Jon Gilbert
MIT Technology Licensing Officer
Patent Protection

Protein Corona Phase Molecular Recognition (CoPhMoRe)

Provisional Patent Application Filed

Protein Corona Phase Molecular Recognition (CoPhMoRe)

PCT Patent Application Filed
Publications
Protein-targeted corona phase molecular recognition
Nature Communications, Jan 8, 2016, Article no. 10241

Applications

This invention is applicable to any research-- industrial, medical, clinical, or otherwise-- that would require high-throughput recognition of a specific biological molecule. It can replace macromolecule purification and detection methods both in vitro and in vivo, such as real-time diagnostics, protein assays such as ELISA or lateral flow strips, immunohistochemistry, and protein-resin binding. It can also be used therapeutically to block receptor-ligand interactions.

Problem Addressed

Currently, the most advanced, widely-used molecular recognition schemes involve natural systems, including antibodies and aptamers. Natural recognition schemes are limited by the need for a living organism or by problems such as degradation, instability, cost, and production scale that natural recognition schemes face. Synthetic recognition schemes such as molecular imprinting have been able to recognize small molecules, but no method for identifying macromolecules has been successful. 

Technology

This invention introduces a novel synthetic recognition scheme for macromolecules that, unlike natural systems, is not constrained by cost or production scale and can withstand long-term storage. The synthetic recognizer is comprised of a single-walled carbon nanotube (SWCNT) with adsorbed surfactant or heteropolymer on its surface. This is achieved through the dialysis of a SWCNT-heteropolymer suspension. The hydrophobic segments of the polymer are adsorbed onto the hydrophobic surface of the SWCNT. This pushes the hydrophilic portions into the surrounding solution, forming a corona phase that is unique to the configuration of the heteropolymer and capable of recognizing target analytes. Previous work has demonstrated that these sensors are capable of recognizing small molecules, such as riboflavin, L-thyroxine, and small neurotransmitters, and a recent screen has suggested that they are also capable of recognizing macromolecules. Of 14 protein analytes and 20 distinct SWCNT corona phases screened, a particular corona phase molecular recognition (CoPhMoRe) scheme using SWCNT suspended in a phospholipid-PEG construct was discovered to be capable of recognizing fibrinogen, a blood plasma macromolecule. Screening for binding was accomplished through detecting spectral changes corresponding to analyte binding, such as fluorescent intensity and emission wavelength modulation, both of which are fast and easy to perform. Atomic force microscopy, quartz crystal microbalance with dissipation measurements, and kinetic measurements all suggest that fibrinogen physically binds to the CoPhMoRe phase through a unique 3D interaction between the conformation of the corona phase and the fibrinogen molecule. Since even such a small screen was capable of identifying the strong binding specificity of a particular corona phase to a macromolecule, future screens will likely identify many other such interactions. 

Advantages

  • High specificity macromolecule recognition 
  • Fast screening for macromolecule binding to corona phase
  • Applicability to in vivo and in vitro screening assays and therapeutics
  • Stable, cost-effective, and mass-producible 
  • Can be applied to small molecule recognition as well