Protein-targeted corona phase molecular recognition

Corona phase molecular recognition (CoPhMoRe) uses a heteropolymer adsorbed onto and templated by a nanoparticle surface to recognize a specific target analyte. This method has not yet been extended to macromolecular analytes, including proteins. Herein we develop a variant of a CoPhMoRe screening procedure of single-walled carbon nanotubes (SWCNT) and use it against a panel of human blood proteins, revealing a specific corona phase that recognizes fibrinogen with high selectivity. In response to fibrinogen binding, SWCNT fluorescence decreases by >80% at saturation. Sequential binding of the three fibrinogen nodules is suggested by selective fluorescence quenching by isolated sub-domains and validated by the quenching kinetics. The fibrinogen recognition also occurs in serum environment, at the clinically relevant fibrinogen concentrations in the human blood. These results open new avenues for synthetic, non-biological antibody analogues that recognize biological macromolecules, and hold great promise for medical and clinical applications.

[1]  D. Mukhopadhyay,et al.  Selective Assembly of DNA-Conjugated Single-Walled Carbon Nanotubes from the Vascular Secretome , 2014, ACS nano.

[2]  Leigh Anderson,et al.  Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins* , 2006, Molecular & Cellular Proteomics.

[3]  N. Anderson,et al.  The Human Plasma Proteome: History, Character, and Diagnostic Prospects , 2003, Molecular & Cellular Proteomics.

[4]  Garrett M. Morris,et al.  Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design , 2001, Science.

[5]  Gengfeng Zheng,et al.  Multiplexed electrical detection of cancer markers with nanowire sensor arrays , 2005, Nature Biotechnology.

[6]  A. Gautier,et al.  C-reactive protein , 2005 .

[7]  C. Milstein,et al.  Continuous cultures of fused cells secreting antibody of predefined specificity , 1975, Nature.

[8]  T W Evans,et al.  Review article: albumin as a drug—biological effects of albumin unrelated to oncotic pressure , 2002, Alimentary pharmacology & therapeutics.

[9]  K. Kobayashi,et al.  Crystal structure of human serum albumin at 2.5 A resolution. , 1999, Protein engineering.

[10]  S. Moestrup,et al.  Structure of the haptoglobin–haemoglobin complex , 2012, Nature.

[11]  Michael S. Strano,et al.  Optical Detection of DNA Conformational Polymorphism on Single-Walled Carbon Nanotubes , 2006, Science.

[12]  R. Smalley,et al.  Structure-Assigned Optical Spectra of Single-Walled Carbon Nanotubes , 2002, Science.

[13]  S. Kishimoto,et al.  Excitonic transition energies in single‐walled carbon nanotubes: Dependence on environmental dielectric constant , 2007 .

[14]  Louis E. Brus,et al.  The Optical Resonances in Carbon Nanotubes Arise from Excitons , 2005, Science.

[15]  Terence E. Rice,et al.  Signaling Recognition Events with Fluorescent Sensors and Switches. , 1997, Chemical reviews.

[16]  R. Doolittle,et al.  Crystal structure of human fibrinogen. , 2009, Biochemistry.

[17]  Y Charles Cao,et al.  Nanomaterials for biomedical applications. , 2008, Nanomedicine.

[18]  M. Strano,et al.  Near-infrared optical sensors based on single-walled carbon nanotubes , 2004, Nature materials.

[19]  Michael S. Strano,et al.  Protein functionalized carbon nanomaterials for biomedical applications , 2015 .

[20]  Cameron Alexander,et al.  Imprinted polymers: artificial molecular recognition materials with applications in synthesis and catalysis , 2003 .

[21]  Nicole M. Iverson,et al.  In Vivo Biosensing Via Tissue Localizable Near Infrared Fluorescent Single Walled Carbon Nanotubes , 2013, Nature nanotechnology.

[22]  J. Vermant,et al.  Directed self-assembly of nanoparticles. , 2010, ACS nano.

[23]  James J Hickman,et al.  A new interpretation of serum albumin surface passivation. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[24]  S. Jayasena.  Aptamers: an emerging class of molecules that rival antibodies in diagnostics. , 1999, Clinical chemistry.

[25]  A. Walton,et al.  A circular dichroism technique for the study of adsorbed protein structure , 1974 .

[26]  Bin Mu,et al.  Neurotransmitter detection using corona phase molecular recognition on fluorescent single-walled carbon nanotube sensors. , 2014, Journal of the American Chemical Society.

[27]  Marcus Textor,et al.  A comparative study of protein adsorption on titanium oxide surfaces using in situ ellipsometry, optical waveguide lightmode spectroscopy, and quartz crystal microbalance/dissipation , 2002 .

[28]  Y. L. Jeyachandran,et al.  Quantitative and qualitative evaluation of adsorption/desorption of bovine serum albumin on hydrophilic and hydrophobic surfaces. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[29]  V. Ribitsch,et al.  Viscoelastic properties of fibrinogen adsorbed onto poly(ethylene terephthalate) surfaces by QCM-D. , 2013, Carbohydrate polymers.

[30]  Shoufang Xu,et al.  Recent advances in molecular imprinting technology: current status, challenges and highlighted applications. , 2011, Chemical Society reviews.

[31]  Harold A Scheraga,et al.  The thrombin-fibrinogen interaction. , 2004, Biophysical chemistry.

[32]  F. Hennrich,et al.  Spectroscopy of single- and double-wall carbon nanotubes in different environments. , 2005, Nano letters.

[33]  M. Loi,et al.  Effect of medium dielectric constant on the physical properties of single-walled carbon nanotubes , 2013 .

[34]  G. Wulff.  Molecular Imprinting in Cross‐Linked Materials with the Aid of Molecular Templates— A Way towards Artificial Antibodies , 1995 .

[35]  G M Anantharamaiah,et al.  Correction for Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation , 2010 .

[36]  Zachary W. Ulissi,et al.  2D equation-of-state model for corona phase molecular recognition on single-walled carbon nanotube and graphene surfaces. , 2015, Langmuir : the ACS journal of surfaces and colloids.

[37]  Eric V Anslyn,et al.  Sensing A Paradigm Shift in the Field of Molecular Recognition: From Selective to Differential Receptors. , 2001, Angewandte Chemie.

[38]  Michael S Strano,et al.  Carbon nanotubes as optical biomedical sensors. , 2013, Advanced drug delivery reviews.

[39]  M. V. Voinova,et al.  Viscoelastic Acoustic Response of Layered Polymer Films at Fluid-Solid Interfaces: Continuum Mechanics Approach , 1998, cond-mat/9805266.

[40]  Steven A Carr,et al.  Protein biomarker discovery and validation: the long and uncertain path to clinical utility , 2006, Nature Biotechnology.

[41]  O Faber,et al.  Insulin Pharmacokinetics , 1984, Diabetes Care.

[42]  Zachary W. Ulissi,et al.  Molecular recognition using corona phase complexes made of synthetic polymers adsorbed on carbon nanotubes , 2013, 2014 40th Annual Northeast Bioengineering Conference (NEBEC).

[43]  Michael S Strano,et al.  A kinetic model for the deterministic prediction of gel-based single-chirality single-walled carbon nanotube separation. , 2013, ACS nano.

[44]  Jennifer N Cha,et al.  Large-area spatially ordered arrays of gold nanoparticles directed by lithographically confined DNA origami. , 2010, Nature nanotechnology.

[45]  Zhuang Liu,et al.  A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. , 2009, Nature nanotechnology.

[46]  S. Suh,et al.  Crystal structure of an uncleaved α1-antitrypsin reveals the conformation of its inhibitory reactive loop , 1995 .

[47]  V. C. Moore,et al.  Band Gap Fluorescence from Individual Single-Walled Carbon Nanotubes , 2002, Science.

[48]  M. Mosesson.  Fibrinogen and fibrin structure and functions , 2005, Journal of thrombosis and haemostasis : JTH.

[49]  Nigel F. Reuel,et al.  Recent advances in molecular recognition based on nanoengineered platforms. , 2014, Accounts of chemical research.

[50]  David Farrar,et al.  Interpretation of protein adsorption: surface-induced conformational changes. , 2005, Journal of the American Chemical Society.

[51]  T. Iba,et al.  [Disseminated intravascular coagulation]. , 2003, Nihon rinsho. Japanese journal of clinical medicine.

[52]  Michael S. Strano,et al.  Chirality dependent corona phase molecular recognition of DNA-wrapped carbon nanotubes , 2015 .

[53]  Y H Chen,et al.  Determination of the helix and beta form of proteins in aqueous solution by circular dichroism. , 1974, Biochemistry.

[54]  F. Almeida,et al.  Structural meta-analysis of regular human insulin in pharmaceutical formulations. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[55]  M. Strano,et al.  Structure and function of glucose binding protein-single walled carbon nanotube complexes. , 2012, Small.

[56]  Steven A Curley,et al.  Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence , 2006, Proceedings of the National Academy of Sciences.

[57]  O. Takai,et al.  SPM analysis of fibrinogen adsorption on solid surfaces , 2007 .

[58]  James N. Weiss.  The Hill equation revisited: uses and misuses , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[59]  Quan Hao,et al.  Iron and bismuth bound human serum transferrin reveals a partially-opened conformation in the N-lobe , 2012, Scientific Reports.

[60]  G. Lowe,et al.  Guidelines on fibrinogen assays , 2003, British journal of haematology.

[61]  N. Anderson,et al.  The Human Plasma Proteome , 2002, Molecular & Cellular Proteomics.

[62]  Gili Bisker,et al.  A Pharmacokinetic Model of a Tissue Implantable Insulin Sensor , 2015, Advanced healthcare materials.

[63]  Gili Bisker,et al.  Mechanism of immobilized protein A binding to immunoglobulin G on nanosensor array surfaces. , 2015, Analytical Chemistry.

[64]  M. Kerr,et al.  Implications of the Near-Planar Solution Structure of Human Myeloma Dimeric IgA1 for Mucosal Immunity and IgA Nephropathy1 , 2008, The Journal of Immunology.

[65]  Thomas A. Horbett,et al.  Chapter 13 Principles underlying the role of adsorbed plasma proteins in blood interactions with foreign materials , 1993 .

[66]  Klaus Schulten,et al.  Comparative Dynamics and Sequence Dependence of DNA and RNA Binding to Single Walled Carbon Nanotubes. , 2015, The journal of physical chemistry. C, Nanomaterials and interfaces.

[67]  M. Strano,et al.  A structure-function relationship for the optical modulation of phenyl boronic acid-grafted, polyethylene glycol-wrapped single-walled carbon nanotubes. , 2012, Journal of the American Chemical Society.

[68]  N. Berova,et al.  Racemic single-walled carbon nanotubes exhibit circular dichroism when wrapped with DNA. , 2006, Journal of the American Chemical Society.

[69]  Raimond B G Ravelli,et al.  The 1.8-A crystal structure of alpha1-acid glycoprotein (Orosomucoid) solved by UV RIP reveals the broad drug-binding activity of this human plasma lipocalin. , 2008, Journal of molecular biology.

[70]  D. C. Harris,et al.  Crystal structure of human chorionic gonadotropin , 1994, Nature.

[71]  N. Weber,et al.  Viscoelastic properties of fibrinogen adsorbed to the surface of biomaterials used in blood-contacting medical devices. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[72]  N. Anderson,et al.  HISTORY, CHARACTER, AND DIAGNOSTIC PROSPECTS* , 2002 .

[73]  M. Strano,et al.  Charge transfer structure-reactivity dependence of fullerene-single-walled carbon nanotube heterojunctions. , 2013, Journal of the American Chemical Society.

[74]  D. Danino.  Cryo-TEM of soft molecular assemblies , 2012 .

[75]  J. Francis,et al.  Mechanisms in Blood Coagulation, Fibrinolysis and the Complement System , 1992 .

[76]  R. Buhmann,et al.  Aptamers—basic research, drug development, and clinical applications , 2005, Applied Microbiology and Biotechnology.

[77]  M. Strano,et al.  Solvatochromism in single-walled carbon nanotubes , 2007 .

[78]  M. Verhovsek,et al.  Laboratory testing for fibrinogen abnormalities , 2008, American journal of hematology.

[79]  G. Braunstein,et al.  Serum human chorionic gonadotropin levels throughout normal pregnancy. , 1976, American journal of obstetrics and gynecology.

[80]  P. Gettins,et al.  Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3. , 2007, The Biochemical journal.

[81]  T. Ugarova,et al.  High-resolution visualization of fibrinogen molecules and fibrin fibers with atomic force microscopy. , 2011, Biomacromolecules.

[82]  M. Mosesson.  The roles of fibrinogen and fibrin in hemostasis and thrombosis. , 1992, Seminars in hematology.

[83]  Nigel F. Reuel,et al.  Experimental Tools to Study Molecular Recognition within the Nanoparticle Corona , 2014, Sensors.

[84]  J. Volanakis,et al.  Three dimensional structure of human C-reactive protein , 1996, Nature Structural Biology.

[85]  S. Hanash,et al.  Mining the plasma proteome for cancer biomarkers , 2008, Nature.

[86]  D. Eisenberg,et al.  Analysis of membrane and surface protein sequences with the hydrophobic moment plot. , 1984, Journal of molecular biology.

[87]  Zachary W. Ulissi,et al.  A Mathematical Formulation and Solution of the CoPhMoRe Inverse Problem for Helically Wrapping Polymer Corona Phases on Cylindrical Substrates , 2015 .

[88]  Clifford A. Hampel,et al.  The encyclopedia of electrochemistry , 1964 .

[89]  Diana Nicoll.  Pocket Guide to Diagnostic Tests , 1992 .

[90]  S. Perkins,et al.  Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation. , 1991, Journal of molecular biology.

[91]  Michael S Strano,et al.  A Ratiometric Sensor Using Single Chirality Near-Infrared Fluorescent Carbon Nanotubes: Application to In Vivo Monitoring. , 2015, Small.

[92]  A. Lees,et al.  Directed assembly metallocyclic supramolecular systems for molecular recognition and chemical sensing , 2008 .