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Home / Equine Research Bank / Nat Commun / Label-free analysis of physiological hyaluronan size distrib...
Nature communications2018; 9(1); 1037; doi: 10.1038/s41467-018-03439-x

Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor.

Abstract: Hyaluronan (or hyaluronic acid, HA) is a ubiquitous molecule that plays critical roles in numerous physiological functions in vivo, including tissue hydration, inflammation, and joint lubrication. Both the abundance and size distribution of HA in biological fluids are recognized as robust indicators of various pathologies and disease progressions. However, such analyses remain challenging because conventional methods are not sufficiently sensitive, have limited dynamic range, and/or are only semi-quantitative. Here we demonstrate label-free detection and molecular weight discrimination of HA with a solid-state nanopore sensor. We first employ synthetic HA polymers to validate the measurement approach and then use the platform to determine the size distribution of as little as 10 ng of HA extracted directly from synovial fluid in an equine model of osteoarthritis. Our results establish a quantitative method for assessment of a significant molecular biomarker that bridges a gap in the current state of the art.
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Publication Date: 2018-03-12 PubMed ID: 29531292PubMed Central: PMC5847568DOI: 10.1038/s41467-018-03439-xGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article discusses a new method for detecting and measuring the molecular weight of Hyaluronan, a critical molecule involved in many bodily functions, using a solid-state nanopore sensor. This technique shows promise for assessing variations in Hyaluronan levels and size distribution, which can indicate different diseases or their progression.

Introduction

  • The focus of this research is Hyaluronan or hyaluronic acid (HA), a molecule prevalent in the body and performs many physiological functions – it contributes to tissue hydration, inflammation response, and joint lubrication.
  • HA level and size distribution in body fluids can serve as indicators of different diseases and their progression. Nonetheless, these analyses have always been a challenge as traditional methods lack sensitivity, have a restricted dynamic range, and only offer semi-quantitative results.

Methodology

  • The researchers propose a method for detecting and determining HA’s molecular weight without any labels, using a solid-state nanopore sensor.
  • They first used synthetic HA polymers to verify this measurement method.

Results & Applications

  • Having validated their approach with synthetic HA, they applied the platform to ascertain the size distribution of HA (minimum 10 ng) that was directly extracted from synovial fluid, using a horse model of osteoarthritis.
  • Their results offer a quantitative method for evaluating a crucial molecular biomarker, thereby, addressing a gap in the current understanding and study.
  • This research holds potential in disease detection and monitoring as variations in hyaluronan levels and size can indicate diverse diseases or their progression states.

Cite This Article

APA
Rivas F, Zahid OK, Reesink HL, Peal BT, Nixon AJ, DeAngelis PL, Skardal A, Rahbar E, Hall AR. (2018). Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor. Nat Commun, 9(1), 1037. https://doi.org/10.1038/s41467-018-03439-x

Publication

Nature communications
ISSN: 2041-1723
NlmUniqueID: 101528555
Country: England
Language: English
Volume: 9
Issue: 1
Pages: 1037
PII: 1037

Researcher Affiliations

Rivas, Felipe
  • Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
Zahid, Osama K
  • Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
Reesink, Heidi L
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Peal, Bridgette T
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Nixon, Alan J
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
DeAngelis, Paul L
  • Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma, OK, 73104, USA.
Skardal, Aleksander
  • Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
  • Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
  • Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Rahbar, Elaheh
  • Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA. erahbar@wakehealth.edu.
Hall, Adam R
  • Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA. arhall@wakehealth.edu.
  • Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA. arhall@wakehealth.edu.
  • Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA. arhall@wakehealth.edu.

MeSH Terms

  • Animals
  • Disease Models, Animal
  • Electrochemical Techniques / instrumentation
  • Electrochemical Techniques / methods
  • Electrophoresis / instrumentation
  • Electrophoresis / methods
  • Horses
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / metabolism
  • Molecular Weight
  • Nanopores
  • Osteoarthritis / metabolism
  • Particle Size
  • Synovial Fluid / chemistry
  • Synovial Fluid / metabolism

Conflict of Interest Statement

A.R.H, E.R., and P.L.D. are listed as inventors on a provisional patent involving the described technology. Remaining authors declare no competing interest.

References

This article includes 55 references
  1. Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover.. J Intern Med 1997 Jul;242(1):27-33.
    doi: 10.1046/j.1365-2796.1997.00170.xpubmed: 9260563google scholar: lookup
  2. Shirali AC, Goldstein DR. Activation of the innate immune system by the endogenous ligand hyaluronan.. Curr Opin Organ Transplant 2008 Feb;13(1):20-5.
    doi: 10.1097/MOT.0b013e3282f3df04pubmed: 18660702google scholar: lookup
  3. Balazs EA, Watson D, Duff IF, Roseman S. Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritis human fluids.. Arthritis Rheum 1967 Aug;10(4):357-76.
    doi: 10.1002/art.1780100407pubmed: 6046018google scholar: lookup
  4. Lokeshwar VB, Obek C, Soloway MS, Block NL. Tumor-associated hyaluronic acid: a new sensitive and specific urine marker for bladder cancer.. Cancer Res 1997 Feb 15;57(4):773-7.
    pubmed: 9044859
  5. Neuman MG, Cohen LB, Nanau RM. Hyaluronic acid as a non-invasive biomarker of liver fibrosis.. Clin Biochem 2016 Feb;49(3):302-15.
    doi: 10.1016/j.clinbiochem.2015.07.019pubmed: 26188920google scholar: lookup
  6. Cowman MK, Lee HG, Schwertfeger KL, McCarthy JB, Turley EA. The Content and Size of Hyaluronan in Biological Fluids and Tissues.. Front Immunol 2015;6:261.
    doi: 10.3389/fimmu.2015.00261pmc: PMC4451640pubmed: 26082778google scholar: lookup
  7. Nakamura K, Yokohama S, Yoneda M, Okamoto S, Tamaki Y, Ito T, Okada M, Aso K, Makino I. High, but not low, molecular weight hyaluronan prevents T-cell-mediated liver injury by reducing proinflammatory cytokines in mice.. J Gastroenterol 2004;39(4):346-54.
    doi: 10.1007/s00535-003-1301-xpubmed: 15168246google scholar: lookup
  8. Noble PW, Lake FR, Henson PM, Riches DW. Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages.. J Clin Invest 1993 Jun;91(6):2368-77.
    doi: 10.1172/JCI116469pmc: PMC443294pubmed: 8514850google scholar: lookup
  9. Rayahin JE, Buhrman JS, Zhang Y, Koh TJ, Gemeinhart RA. High and low molecular weight hyaluronic acid differentially influence macrophage activation.. ACS Biomater Sci Eng 2015 Jul 13;1(7):481-493.
    doi: 10.1021/acsbiomaterials.5b00181pmc: PMC4533115pubmed: 26280020google scholar: lookup
  10. Sasaki Y, Uzuki M, Nohmi K, Kitagawa H, Kamataki A, Komagamine M, Murakami K, Sawai T. Quantitative measurement of serum hyaluronic acid molecular weight in rheumatoid arthritis patients and the role of hyaluronidase.. Int J Rheum Dis 2011 Oct;14(4):313-9.
    doi: 10.1111/j.1756-185X.2011.01683.xpubmed: 22004226google scholar: lookup
  11. Haserodt S, Aytekin M, Dweik RA. A comparison of the sensitivity, specificity, and molecular weight accuracy of three different commercially available Hyaluronan ELISA-like assays.. Glycobiology 2011 Feb;21(2):175-83.
    doi: 10.1093/glycob/cwq145pubmed: 20864567google scholar: lookup
  12. Hokputsa S, Jumel K, Alexander C, Harding SE. A comparison of molecular mass determination of hyaluronic acid using SEC/MALLS and sedimentation equilibrium.. Eur Biophys J 2003 Aug;32(5):450-6.
    doi: 10.1007/s00249-003-0299-6pubmed: 12698289google scholar: lookup
  13. Yeung B, Marecak D. Molecular weight determination of hyaluronic acid by gel filtration chromatography coupled to matrix-assisted laser desorption ionization mass spectrometry.. J Chromatogr A 1999 Aug 13;852(2):573-81.
    doi: 10.1016/S0021-9673(99)00647-0pubmed: 10481993google scholar: lookup
  14. Kühn AV, Raith K, Sauerland V, Neubert RH. Quantification of hyaluronic acid fragments in pharmaceutical formulations using LC-ESI-MS.. J Pharm Biomed Anal 2003 Jan 1;30(5):1531-7.
    doi: 10.1016/S0731-7085(02)00544-7pubmed: 12467925google scholar: lookup
  15. Volpi N. On-line HPLC/ESI-MS separation and characterization of hyaluronan oligosaccharides from 2-mers to 40-mers.. Anal Chem 2007 Aug 15;79(16):6390-7.
    doi: 10.1021/ac070837dpubmed: 17608452google scholar: lookup
  16. Bhilocha S, Amin R, Pandya M, Yuan H, Tank M, LoBello J, Shytuhina A, Wang W, Wisniewski HG, de la Motte C, Cowman MK. Agarose and polyacrylamide gel electrophoresis methods for molecular mass analysis of 5- to 500-kDa hyaluronan.. Anal Biochem 2011 Oct 1;417(1):41-9.
    doi: 10.1016/j.ab.2011.05.026pmc: PMC3207642pubmed: 21684248google scholar: lookup
  17. Cowman MK, Chen CC, Pandya M, Yuan H, Ramkishun D, LoBello J, Bhilocha S, Russell-Puleri S, Skendaj E, Mijovic J, Jing W. Improved agarose gel electrophoresis method and molecular mass calculation for high molecular mass hyaluronan.. Anal Biochem 2011 Oct 1;417(1):50-6.
    doi: 10.1016/j.ab.2011.05.023pubmed: 21683677google scholar: lookup
  18. Li J, Stein D, McMullan C, Branton D, Aziz MJ, Golovchenko JA. Ion-beam sculpting at nanometre length scales.. Nature 2001 Jul 12;412(6843):166-9.
    doi: 10.1038/35084037pubmed: 11449268google scholar: lookup
  19. Storm AJ, Chen JH, Ling XS, Zandbergen HW, Dekker C. Fabrication of solid-state nanopores with single-nanometre precision.. Nat Mater 2003 Aug;2(8):537-40.
    doi: 10.1038/nmat941pubmed: 12858166google scholar: lookup
  20. Fennouri A, Przybylski C, Pastoriza-Gallego M, Bacri L, Auvray L, Daniel R. Single molecule detection of glycosaminoglycan hyaluronic acid oligosaccharides and depolymerization enzyme activity using a protein nanopore.. ACS Nano 2012 Nov 27;6(11):9672-8.
    doi: 10.1021/nn3031047pubmed: 23046010google scholar: lookup
  21. Fennouri A, Daniel R, Pastoriza-Gallego M, Auvray L, Pelta J, Bacri L. Kinetics of enzymatic degradation of high molecular weight polysaccharides through a nanopore: experiments and data-modeling.. Anal Chem 2013 Sep 17;85(18):8488-92.
    doi: 10.1021/ac4020929pubmed: 23992452google scholar: lookup
  22. Gatej I, Popa M, Rinaudo M. Role of the pH on hyaluronan behavior in aqueous solution.. Biomacromolecules 2005 Jan-Feb;6(1):61-7.
    doi: 10.1021/bm040050mpubmed: 15638505google scholar: lookup
  23. Firnkes M, Pedone D, Knezevic J, Döblinger M, Rant U. Electrically facilitated translocations of proteins through silicon nitride nanopores: conjoint and competitive action of diffusion, electrophoresis, and electroosmosis.. Nano Lett 2010 Jun 9;10(6):2162-7.
    doi: 10.1021/nl100861cpubmed: 20438117google scholar: lookup
  24. Gershow M, Golovchenko JA. Recapturing and trapping single molecules with a solid-state nanopore.. Nat Nanotechnol 2007 Dec;2(12):775-9.
    doi: 10.1038/nnano.2007.381pmc: PMC3174059pubmed: 18654430google scholar: lookup
  25. Li J, Gershow M, Stein D, Brandin E, Golovchenko JA. DNA molecules and configurations in a solid-state nanopore microscope.. Nat Mater 2003 Sep;2(9):611-5.
    doi: 10.1038/nmat965pubmed: 12942073google scholar: lookup
  26. Storm AJ, Chen JH, Zandbergen HW, Dekker C. Translocation of double-strand DNA through a silicon oxide nanopore.. Phys Rev E Stat Nonlin Soft Matter Phys 2005 May;71(5 Pt 1):051903.
    doi: 10.1103/PhysRevE.71.051903pubmed: 16089567google scholar: lookup
  27. Storm AJ, Storm C, Chen J, Zandbergen H, Joanny JF, Dekker C. Fast DNA translocation through a solid-state nanopore.. Nano Lett 2005 Jul;5(7):1193-7.
    doi: 10.1021/nl048030dpubmed: 16178209google scholar: lookup
  28. Fologea D, Gershow M, Ledden B, McNabb DS, Golovchenko JA, Li J. Detecting single stranded DNA with a solid state nanopore.. Nano Lett 2005 Oct;5(10):1905-9.
    doi: 10.1021/nl051199mpmc: PMC2543124pubmed: 16218707google scholar: lookup
  29. Wanunu M, Morrison W, Rabin Y, Grosberg AY, Meller A. Electrostatic focusing of unlabelled DNA into nanoscale pores using a salt gradient.. Nat Nanotechnol 2010 Feb;5(2):160-5.
    doi: 10.1038/nnano.2009.379pmc: PMC2849735pubmed: 20023645google scholar: lookup
  30. Grosberg AY, Rabin Y. DNA capture into a nanopore: interplay of diffusion and electrohydrodynamics.. J Chem Phys 2010 Oct 28;133(16):165102.
    doi: 10.1063/1.3495481pubmed: 21033823google scholar: lookup
  31. Wanunu M, Dadosh T, Ray V, Jin J, McReynolds L, Drndić M. Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors.. Nat Nanotechnol 2010 Nov;5(11):807-14.
    doi: 10.1038/nnano.2010.202pubmed: 20972437google scholar: lookup
  32. Zahid OK, Zhao BS, He C, Hall AR. Quantifying mammalian genomic DNA hydroxymethylcytosine content using solid-state nanopores.. Sci Rep 2016 Jul 7;6:29565.
    doi: 10.1038/srep29565pmc: PMC4935868pubmed: 27383905google scholar: lookup
  33. Jing W, DeAngelis PL. Synchronized chemoenzymatic synthesis of monodisperse hyaluronan polymers.. J Biol Chem 2004 Oct 1;279(40):42345-9.
    doi: 10.1074/jbc.M402744200pubmed: 15299014google scholar: lookup
  34. Rosenstein JK, Wanunu M, Merchant CA, Drndic M, Shepard KL. Integrated nanopore sensing platform with sub-microsecond temporal resolution.. Nat Methods 2012 Mar 18;9(5):487-92.
    doi: 10.1038/nmeth.1932pmc: PMC3648419pubmed: 22426489google scholar: lookup
  35. Ferrari M, Bloomfield V. Scattering and diffusion of mononucleosomal DNA - effects of counterion valence and salt and DNA concentration.. Macromolecules 1992;25:5266–5276.
    doi: 10.1021/ma00046a025google scholar: lookup
  36. Litwiniuk M, Krejner A, Speyrer MS, Gauto AR, Grzela T. Hyaluronic Acid in Inflammation and Tissue Regeneration.. Wounds 2016 Mar;28(3):78-88.
    pubmed: 26978861
  37. Band PA, Heeter J, Wisniewski HG, Liublinska V, Pattanayak CW, Karia RJ, Stabler T, Balazs EA, Kraus VB. Hyaluronan molecular weight distribution is associated with the risk of knee osteoarthritis progression.. Osteoarthritis Cartilage 2015 Jan;23(1):70-6.
    doi: 10.1016/j.joca.2014.09.017pmc: PMC4375131pubmed: 25266961google scholar: lookup
  38. Hui AY, McCarty WJ, Masuda K, Firestein GS, Sah RL. A systems biology approach to synovial joint lubrication in health, injury, and disease.. Wiley Interdiscip Rev Syst Biol Med 2012 Jan-Feb;4(1):15-37.
    doi: 10.1002/wsbm.157pmc: PMC3593048pubmed: 21826801google scholar: lookup
  39. Seyfried NT, McVey GF, Almond A, Mahoney DJ, Dudhia J, Day AJ. Expression and purification of functionally active hyaluronan-binding domains from human cartilage link protein, aggrecan and versican: formation of ternary complexes with defined hyaluronan oligosaccharides.. J Biol Chem 2005 Feb 18;280(7):5435-48.
    doi: 10.1074/jbc.M411297200pubmed: 15590670google scholar: lookup
  40. Day AJ, Prestwich GD. Hyaluronan-binding proteins: tying up the giant.. J Biol Chem 2002 Feb 15;277(7):4585-8.
    doi: 10.1074/jbc.R100036200pubmed: 11717315google scholar: lookup
  41. Barker SA, Hawkins CF, Hewins M. Mucopolysaccharides in synovial fluid detection of chondroitin sulphate.. Ann Rheum Dis 1966 May;25(3):209-13.
    doi: 10.1136/ard.25.3.209pmc: PMC2453397pubmed: 4222610google scholar: lookup
  42. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  43. Temple-Wong MM, Ren S, Quach P, Hansen BC, Chen AC, Hasegawa A, D'Lima DD, Koziol J, Masuda K, Lotz MK, Sah RL. Hyaluronan concentration and size distribution in human knee synovial fluid: variations with age and cartilage degeneration.. Arthritis Res Ther 2016 Jan 21;18:18.
    doi: 10.1186/s13075-016-0922-4pmc: PMC4721052pubmed: 26792492google scholar: lookup
  44. Chan DD, Xiao WF, Li J, de la Motte CA, Sandy JD, Plaas A. Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage.. Osteoarthritis Cartilage 2015 Nov;23(11):1879-89.
    doi: 10.1016/j.joca.2015.06.021pmc: PMC4630789pubmed: 26521733google scholar: lookup
  45. Laurent TC, Laurent UB, Fraser JR. Serum hyaluronan as a disease marker.. Ann Med 1996 Jun;28(3):241-53.
    doi: 10.3109/07853899609033126pubmed: 8811168google scholar: lookup
  46. Tomatsu S, Montaño AM, Oguma T, Dung VC, Oikawa H, de Carvalho TG, Gutiérrez ML, Yamaguchi S, Suzuki Y, Fukushi M, Sakura N, Barrera L, Kida K, Kubota M, Orii T. Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I.. J Inherit Metab Dis 2010 Apr;33(2):141-50.
    doi: 10.1007/s10545-009-9036-3pubmed: 20162367google scholar: lookup
  47. Hayes AJ, Tudor D, Nowell MA, Caterson B, Hughes CE. Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells.. J Histochem Cytochem 2008 Feb;56(2):125-38.
    doi: 10.1369/jhc.7A7320.2007pmc: PMC2324172pubmed: 17938280google scholar: lookup
  48. Kubaski F. Di-sulfated keratan sulfate as a novel biomarker for mucopolysaccharidosis IVA.. Mol. Genet. Metab. 2015;114:S66–S67.
  49. Lee HG, Cowman MK. An agarose gel electrophoretic method for analysis of hyaluronan molecular weight distribution.. Anal Biochem 1994 Jun;219(2):278-87.
    doi: 10.1006/abio.1994.1267pubmed: 8080084google scholar: lookup
  50. Yuan H, Amin R, Ye X, de la Motte CA, Cowman MK. Determination of hyaluronan molecular mass distribution in human breast milk.. Anal Biochem 2015 Apr 1;474:78-88.
    doi: 10.1016/j.ab.2014.12.020pmc: PMC4357551pubmed: 25579786google scholar: lookup
  51. Collins TJ. ImageJ for microscopy.. Biotechniques 2007 Jul;43(1 Suppl):25-30.
    doi: 10.2144/000112517pubmed: 17936939google scholar: lookup
  52. Yang J, Ferranti DC, Stern LA, Sanford CA, Huang J, Ren Z, Qin LC, Hall AR. Rapid and precise scanning helium ion microscope milling of solid-state nanopores for biomolecule detection.. Nanotechnology 2011 Jul 15;22(28):285310.
    doi: 10.1088/0957-4484/22/28/285310pubmed: 21659692google scholar: lookup
  53. Haynes, W. M. CRC Handbook of Chemistry and Physics, 97th Edition. (CRC Press, Boca Raton, FL, 2016)
  54. Kowalczyk SW, Wells DB, Aksimentiev A, Dekker C. Slowing down DNA translocation through a nanopore in lithium chloride.. Nano Lett 2012 Feb 8;12(2):1038-44.
    doi: 10.1021/nl204273hpmc: PMC3349906pubmed: 22229707google scholar: lookup
  55. Uram JD, Ke K, Mayer M. Noise and bandwidth of current recordings from submicrometer pores and nanopores.. ACS Nano 2008 May;2(5):857-72.
    doi: 10.1021/nn700322mpubmed: 19206482google scholar: lookup

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  1. Nguyen L, Lin X, Verma S, Puri S, Hascall V, Gesteira TF, Coulson-Thomas VJ. Characterization of the Molecular Weight of Hyaluronan in Eye Products Using a Novel Method of Size Exclusion High-Pressure Liquid Chromatography. Transl Vis Sci Technol 2023 Apr 3;12(4):13.
    doi: 10.1167/tvst.12.4.13pubmed: 37052911google scholar: lookup
  2. Perez S, Makshakova O, Angulo J, Bedini E, Bisio A, de Paz JL, Fadda E, Guerrini M, Hricovini M, Hricovini M, Lisacek F, Nieto PM, Pagel K, Paiardi G, Richter R, Samsonov SA, Vivès RR, Nikitovic D, Ricard Blum S. Glycosaminoglycans: What Remains To Be Deciphered?. JACS Au 2023 Mar 27;3(3):628-656.
    doi: 10.1021/jacsau.2c00569pubmed: 37006755google scholar: lookup
  3. Li M, Xiong Y, Cao Y, Zhang C, Li Y, Ning H, Liu F, Zhou H, Li X, Ye X, Pang Y, Zhang J, Liang X, Qing G. Identification of tagged glycans with a protein nanopore. Nat Commun 2023 Mar 28;14(1):1737.
    doi: 10.1038/s41467-023-37348-5pubmed: 36977665google scholar: lookup
  4. Barrueta Tenhunen A, van der Heijden J, Dogné S, Flamion B, Weigl W, Frithiof R, Skorup P, Larsson A, Larsson A, Tenhunen J. HIGH-MOLECULAR-WEIGHT HYALURONAN-A POTENTIAL ADJUVANT TO FLUID RESUSCITATION IN ABDOMINAL SEPSIS?. Shock 2023 May 1;59(5):763-770.
    doi: 10.1097/SHK.0000000000002089pubmed: 36809365google scholar: lookup
  5. Zheng K, Bai J, Yang H, Xu Y, Pan G, Wang H, Geng D. Nanomaterial-assisted theranosis of bone diseases. Bioact Mater 2023 Jun;24:263-312.
    doi: 10.1016/j.bioactmat.2022.12.014pubmed: 36632509google scholar: lookup
  6. Liu L, Xu Z, Awayda K, Dollery SJ, Bao M, Fan J, Cormier D, O'Connell M, Tobin GJ, Du K. Gold Nanoparticle-Labeled CRISPR-Cas13a Assay for the Sensitive Solid-State Nanopore Molecular Counting. Adv Mater Technol 2022 Mar;7(3).
    doi: 10.1002/admt.202101550pubmed: 36338309google scholar: lookup
  7. Bayat P, Rambaud C, Priem B, Bourderioux M, Bilong M, Poyer S, Pastoriza-Gallego M, Oukhaled A, Mathé J, Daniel R. Comprehensive structural assignment of glycosaminoglycan oligo- and polysaccharides by protein nanopore. Nat Commun 2022 Aug 30;13(1):5113.
    doi: 10.1038/s41467-022-32800-4pubmed: 36042212google scholar: lookup
  8. Srimasorn S, Souter L, Green DE, Djerbal L, Goodenough A, Duncan JA, Roberts ARE, Zhang X, Débarre D, DeAngelis PL, Kwok JCF, Richter RP. A quartz crystal microbalance method to quantify the size of hyaluronan and other glycosaminoglycans on surfaces. Sci Rep 2022 Jun 29;12(1):10980.
    doi: 10.1038/s41598-022-14948-7pubmed: 35768463google scholar: lookup
  9. MacLeod R, Chan FV, Yuan H, Ye X, Sin YJA, Vitelli TM, Cucu T, Leung A, Baljak I, Osinski S, Fu Y, Jung GID, Amar A, DeAngelis PL, Hellman U, Cowman MK. Selective isolation of hyaluronan by solid phase adsorption to silica. Anal Biochem 2022 Sep 1;652:114769.
    doi: 10.1016/j.ab.2022.114769pubmed: 35660507google scholar: lookup
  10. Rivas F, Erxleben D, Smith I, Rahbar E, DeAngelis PL, Cowman MK, Hall AR. Methods for isolating and analyzing physiological hyaluronan: a review. Am J Physiol Cell Physiol 2022 Apr 1;322(4):C674-C687.
    doi: 10.1152/ajpcell.00019.2022pubmed: 35196167google scholar: lookup
  11. Fasanello DC, Su J, Deng S, Yin R, Colville MJ, Berenson JM, Kelly CM, Freer H, Rollins A, Wagner B, Rivas F, Hall AR, Rahbar E, DeAngelis PL, Paszek MJ, Reesink HL. Hyaluronic acid synthesis, degradation, and crosslinking in equine osteoarthritis: TNF-α-TSG-6-mediated HC-HA formation. Arthritis Res Ther 2021 Aug 20;23(1):218.
    doi: 10.1186/s13075-021-02588-7pubmed: 34416923google scholar: lookup
  12. Li M, Xiong Y, Wang D, Liu Y, Na B, Qin H, Liu J, Liang X, Qing G. Biomimetic nanochannels for the discrimination of sialylated glycans via a tug-of-war between glycan binding and polymer shrinkage. Chem Sci 2019 Dec 3;11(3):748-756.
    doi: 10.1039/c9sc05319kpubmed: 34123048google scholar: lookup
  13. Zahid OK, Rivas F, Wang F, Sethi K, Reiss K, Bearden S, Hall AR. Solid-state nanopore analysis of human genomic DNA shows unaltered global 5-hydroxymethylcytosine content associated with early-stage breast cancer. Nanomedicine 2021 Jul;35:102407.
    doi: 10.1016/j.nano.2021.102407pubmed: 33905828google scholar: lookup
  14. Cai Y, Zhang B, Liang L, Wang S, Zhang L, Wang L, Cui HL, Zhou Y, Wang D. A solid-state nanopore-based single-molecule approach for label-free characterization of plant polysaccharides. Plant Commun 2021 Mar 8;2(2):100106.
    doi: 10.1016/j.xplc.2020.100106pubmed: 33898974google scholar: lookup
  15. Xia K, Hagan JT, Fu L, Sheetz BS, Bhattacharya S, Zhang F, Dwyer JR, Linhardt RJ. Synthetic heparan sulfate standards and machine learning facilitate the development of solid-state nanopore analysis. Proc Natl Acad Sci U S A 2021 Mar 16;118(11).
    doi: 10.1073/pnas.2022806118pubmed: 33688052google scholar: lookup
  16. Amargant F, Manuel SL, Tu Q, Parkes WS, Rivas F, Zhou LT, Rowley JE, Villanueva CE, Hornick JE, Shekhawat GS, Wei JJ, Pavone ME, Hall AR, Pritchard MT, Duncan FE. Ovarian stiffness increases with age in the mammalian ovary and depends on collagen and hyaluronan matrices. Aging Cell 2020 Nov;19(11):e13259.
    doi: 10.1111/acel.13259pubmed: 33079460google scholar: lookup
  17. Song Y, Zhang F, Linhardt RJ. Analysis of the Glycosaminoglycan Chains of Proteoglycans. J Histochem Cytochem 2021 Feb;69(2):121-135.
    doi: 10.1369/0022155420937154pubmed: 32623943google scholar: lookup
  18. Hagan JT, Sheetz BS, Bandara YMNDY, Karawdeniya BI, Morris MA, Chevalier RB, Dwyer JR. Chemically tailoring nanopores for single-molecule sensing and glycomics. Anal Bioanal Chem 2020 Oct;412(25):6639-6654.
    doi: 10.1007/s00216-020-02717-2pubmed: 32488384google scholar: lookup
  19. Mohammadinejad R, Ashrafizadeh M, Pardakhty A, Uzieliene I, Denkovskij J, Bernotiene E, Janssen L, Lorite GS, Saarakkala S, Mobasheri A. Nanotechnological Strategies for Osteoarthritis Diagnosis, Monitoring, Clinical Management, and Regenerative Medicine: Recent Advances and Future Opportunities. Curr Rheumatol Rep 2020 Apr 4;22(4):12.
    doi: 10.1007/s11926-020-0884-zpubmed: 32248371google scholar: lookup
  20. Peal BT, Gagliardi R, Su J, Fortier LA, Delco ML, Nixon AJ, Reesink HL. Synovial fluid lubricin and hyaluronan are altered in equine osteochondral fragmentation, cartilage impact injury, and full-thickness cartilage defect models. J Orthop Res 2020 Aug;38(8):1826-1835.
    doi: 10.1002/jor.24597pubmed: 31965593google scholar: lookup
  21. Wei W, Faubel JL, Selvakumar H, Kovari DT, Tsao J, Rivas F, Mohabir AT, Krecker M, Rahbar E, Hall AR, Filler MA, Washburn JL, Weigel PH, Curtis JE. Self-regenerating giant hyaluronan polymer brushes. Nat Commun 2019 Dec 4;10(1):5527.
    doi: 10.1038/s41467-019-13440-7pubmed: 31797934google scholar: lookup
  22. Kumar Sharma R, Agrawal I, Dai L, Doyle PS, Garaj S. Complex DNA knots detected with a nanopore sensor. Nat Commun 2019 Oct 2;10(1):4473.
    doi: 10.1038/s41467-019-12358-4pubmed: 31578328google scholar: lookup
  23. Bearden S, Wang F, Hall AR. Simple and Efficient Room-Temperature Release of Biotinylated Nucleic Acids from Streptavidin and Its Application to Selective Molecular Detection. Anal Chem 2019 Jul 2;91(13):7996-8001.
    doi: 10.1021/acs.analchem.9b01873pubmed: 31144812google scholar: lookup
  24. Fennouri A, Ramiandrisoa J, Bacri L, Mathé J, Daniel R. Comparative biosensing of glycosaminoglycan hyaluronic acid oligo- and polysaccharides using aerolysin and [Formula: see text]-hemolysin nanopores(⋆). Eur Phys J E Soft Matter 2018 Oct 23;41(10):127.
    doi: 10.1140/epje/i2018-11733-5pubmed: 30338424google scholar: lookup
  25. Karawdeniya BI, Bandara YMNDY, Nichols JW, Chevalier RB, Dwyer JR. Surveying silicon nitride nanopores for glycomics and heparin quality assurance. Nat Commun 2018 Aug 16;9(1):3278.
    doi: 10.1038/s41467-018-05751-ypubmed: 30115917google scholar: lookup
  26. Xiao Y, Zhang S, Gao X, Li T, Zhang H, Zhang P, Huang S. Nanopore profiling and structure determination of oligosaccharides by fragmentation. Sci Adv 2026 Jan 2;12(1):eaea8462.
    doi: 10.1126/sciadv.aea8462pubmed: 41477834google scholar: lookup
  27. Peters A, Yasuhara K, Su W, Matsumoto S, Pham P, Banine F, Harris E, Back SA, Sherman LS. The CEMIP Hyaluronidase is Elevated in Oligodendrocyte Progenitor Cells and Inhibits Oligodendrocyte Maturation. ASN Neuro 2025;17(1):2600157.
    doi: 10.1080/17590914.2025.2600157pubmed: 41361922google scholar: lookup
  28. Kawasaki T, Zen H, Nogami K, Hayakawa K, Sakai T, Hayakawa Y. Direct Analysis of Solid-Phase Carbohydrate Polymers by Infrared Multiphoton Dissociation Reaction Combined with Synchrotron Radiation Infrared Microscopy and Electrospray Ionization Mass Spectrometry. Polymers (Basel) 2025 Aug 22;17(17).
    doi: 10.3390/polym17172273pubmed: 40942191google scholar: lookup
  29. McCracken JM, Calderon GA, Rivas F, Erxleben D, Moseley T, Kumar LA, Kennedy DE 2nd, Balaji S, Hall A, Hakim JCE. Unveiling Vaginal Fibrosis: A Novel Murine Model Using Bleomycin and Epithelial Disruption. Open J Obstet Gynecol 2025 Mar;15(3):371-386.
    doi: 10.4236/ojog.2025.153033pubmed: 40895506google scholar: lookup
  30. Chen C, Zhang X, Zhang W, Ding D, Loka RS, Zhao K, Ling P, Wang S. Dermatan Sulfate: Structure, Biosynthesis, and Biological Roles. Biomolecules 2025 Aug 12;15(8).
    doi: 10.3390/biom15081158pubmed: 40867602google scholar: lookup
  31. Elaguech MA, Sethi K, Hall AR. Solid-state nanopore quantification of discrete sequence motifs from DNA and RNA targets in human plasma. Analyst 2025 Jul 21;150(15):3400-3407.
    doi: 10.1039/d5an00373cpubmed: 40560043google scholar: lookup
  32. Michaut A, Mongera A, Gupta A, Tarazona OA, Serra M, Kefala GM, Rigoni P, Lee JG, Rivas F, Hall AR, Mahadevan L, Guevorkian K, Pourquié O. Extracellular volume expansion drives vertebrate axis elongation. Curr Biol 2025 Feb 24;35(4):843-853.e6.
    doi: 10.1016/j.cub.2024.12.051pubmed: 39879975google scholar: lookup
  33. Erxleben DA, Rivas F, Smith I, Poddar S, DeAngelis PL, Rahbar E, Hall AR. High-fidelity and iterative affinity extraction of hyaluronan. Proteoglycan Res 2024 Oct-Dec;2(4):e70008.
    doi: 10.1002/pgr2.70008pubmed: 39650564google scholar: lookup
  34. Yin B, Xie W, Fang S, He S, Ma W, Liang L, Yin Y, Zhou D, Wang Z, Wang D. Research Progress on Saccharide Molecule Detection Based on Nanopores. Sensors (Basel) 2024 Aug 22;24(16).
    doi: 10.3390/s24165442pubmed: 39205136google scholar: lookup
  35. Kizer ME, R Dwyer J. Editors' Choice-Perspective-Deciphering the Glycan Kryptos by Solid-State Nanopore Single-Molecule Sensing: A Call for Integrated Advancements Across Glyco- and Nanopore Science. ECS Sens Plus 2024 Jun 3;3(2):020604.
    doi: 10.1149/2754-2726/ad49b0pubmed: 38799647google scholar: lookup
  36. Yao G, Ke W, Xia B, Gao Z. Nanopore-based glycan sequencing: state of the art and future prospects. Chem Sci 2024 May 1;15(17):6229-6243.
    doi: 10.1039/d4sc01466apubmed: 38699252google scholar: lookup
  37. Dorey A, Howorka S. Nanopore DNA sequencing technologies and their applications towards single-molecule proteomics. Nat Chem 2024 Mar;16(3):314-334.
    doi: 10.1038/s41557-023-01322-xpubmed: 38448507google scholar: lookup
  38. Patiño-Guillén G, Pešović J, Panić M, Savić-Pavićević D, Bošković F, Keyser UF. Single-molecule RNA sizing enables quantitative analysis of alternative transcription termination. Nat Commun 2024 Feb 24;15(1):1699.
    doi: 10.1038/s41467-024-45968-8pubmed: 38402271google scholar: lookup
  39. Erxleben DA, Dodd RJ, Day AJ, Green DE, DeAngelis PL, Poddar S, Enghild JJ, Huebner JL, Kraus VB, Watkins AR, Reesink HL, Rahbar E, Hall AR. Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores. Anal Chem 2024 Jan 30;96(4):1606-1613.
    doi: 10.1021/acs.analchem.3c04387pubmed: 38215004google scholar: lookup
  40. Fan X, Sato Y, Shiraki Y, Nishizawa S. Design of synthetic peptide-based fluorescence probes for turn-on detection of hyaluronan. Anal Sci 2024 Apr;40(4):609-614.
    doi: 10.1007/s44211-023-00491-6pubmed: 38214835google scholar: lookup
  41. Verma S, Moreno IY, Sun M, Gesteira TF, Coulson-Thomas VJ. Age related changes in hyaluronan expression leads to Meibomian gland dysfunction. Matrix Biol 2023 Dec;124:23-38.
    doi: 10.1016/j.matbio.2023.11.002pubmed: 37949327google scholar: lookup
  42. Babayev E, Suebthawinkul C, Gokyer D, Parkes WS, Rivas F, Pavone ME, Hall AR, Pritchard MT, Duncan FE. Cumulus expansion is impaired with advanced reproductive age due to loss of matrix integrity and reduced hyaluronan. Aging Cell 2023 Nov;22(11):e14004.
    doi: 10.1111/acel.14004pubmed: 37850336google scholar: lookup
  43. de Jong IEM, Hunt ML, Chen D, Du Y, Llewellyn J, Gupta K, Li D, Erxleben D, Rivas F, Hall AR, Furth EE, Naji A, Liu C, Dhand A, Burdick JA, Davey MG, Flake AW, Porte RJ, Russo PA, Gaynor JW, Wells RG. A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia. J Hepatol 2023 Dec;79(6):1396-1407.
    doi: 10.1016/j.jhep.2023.08.010pubmed: 37611641google scholar: lookup
  44. Hagan JT, Gonzalez A, Shi Y, Han GGD, Dwyer JR. Photoswitchable Binary Nanopore Conductance and Selective Electronic Detection of Single Biomolecules under Wavelength and Voltage Polarity Control. ACS Nano 2022 Apr 26;16(4):5537-5544.
    doi: 10.1021/acsnano.1c10039pubmed: 35286058google scholar: lookup
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