Abstract
Polysaccharides have been extensively studied as biomaterials in various fields for their biocompatibility, biodegradability, and biological functions. To obtain water-insoluble materials from polysaccharides, polyion complexes (PICs) formed between cationic and anionic polysaccharides have been widely used in drug delivery systems and tissue engineering. Understanding the atomic interaction mechanism of oppositely charged polysaccharides is important in the design and application of PIC-based materials. In this work, the interaction between single-stranded chitosan and four kinds of anionic oligosaccharides was systematically investigated to elucidate the effects of the functional groups of chitosan and chemical species of anionic oligosaccharides on complex formation using molecular dynamics (MD) simulation with atomic detail. We verified that chitosan and anionic oligosaccharides form complexes, regardless of the functional groups of chitosan. For ‒NH3+ chitosan, due to the strong electrostatic interaction, a higher number of hydrogen bonds between ‒NH3+ in chitosan and anionic charged groups of anionic oligosaccharides were formed. Our results also suggested that ‒NH2 and ‒NHAc chitosan could form complexes with anionic oligosaccharides due to hydrogen bonds. These findings might be important for the design and stabilization of PICs based on polysaccharides.
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References
Salbach J, Rachner TD, Rauner M, Hempel U, Anderegg U, Franz S, et al. Regenerative potential of glycosaminoglycans for skin and bone. J Mol Med. 2012;90:625–35.
Sood A, Gupta A, Agrawal G. Recent advances in polysaccharides based biomaterials for drug delivery and tissue engineering applications. Carbohydr Polym Technol Appl. 2021;2:100067.
Shelke NB, James R, Laurencin CT, Kumbar SG. Polysaccharide biomaterials for drug delivery and regenerative engineering. Polym Adv Technol. 2014;25:448–60.
Tzianabos AO. Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin Microbiol Rev. 2000;13:523–33.
Suh JK, Matthew HW. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials. 2000;21:2589–98.
Cardin AD, Weintraub HJ. Molecular modeling of protein-glycosaminoglycan interactions. Arteriosclerosis. 1989;9:21–32.
Sugahara K, Mikami T, Uyama T, Mizuguchi S, Nomura K, Kitagawa H. Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate. Curr Opin Struct Biol. 2003;13:612–20.
Volpi N. Quality of different chondroitin sulfate preparations in relation to their therapeutic activity. J Pharm Pharm. 2009;61:1271–80.
Necas J, Bartosikoval L, Brauner P, Kolar J. Hyaluronic acid (hyaluronan): a review. Vet Med. 2008;53:397–411.
Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004;4:528–39.
Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater. 2011;23:H41–56.
Sugahara K, Kitagawa H. Heparin and heparan sulfate biosynthesis. IUBMB Life. 2002;54:163–75.
Capila I, Linhardt RJ. Heparin-protein interactions. Angew Chem Int Ed Engl. 2002;41:391–412.
Capanema NSV, Mansur AAP, de Jesus AC, Carvalho SM, de Oliveira LC, Mansur HS. Superabsorbent crosslinked carboxymethyl cellulose-PEG hydrogels for potential wound dressing applications. Int J Biol Macromol. 2018;106:1218–34.
Reza AT, Nicoll SB. Characterization of novel photocrosslinked carboxymethylcellulose hydrogels for encapsulation of nucleus pulposus cells. Acta Biomater. 2010;6:179–86.
Ogushi Y, Sakai S, Kawakami K. Synthesis of enzymatically-gellable carboxymethylcellulose for biomedical applications. J Biosci Bioeng. 2007;104:30–3.
Croisier F, Jérôme C. Chitosan-based biomaterials for tissue engineering. Eur Polym J. 2013;49:780–92.
Kim IY, Seo SJ, Moon HS, Yoo MK, Park IY, Kim BC, et al. Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv. 2008;26:1–21.
Luo Y, Wang Q. Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery. Int J Biol Macromol. 2014;64:353–67.
Rodrigues MN, Oliveira MB, Costa RR, Mano JF. Chitosan/chondroitin sulfate membranes produced by polyelectrolyte complexation for cartilage engineering. Biomacromolecules. 2016;17:2178–88.
Sharma S, Swetha KL, Roy A. Chitosan-chondroitin sulfate based polyelectrolyte complex for effective management of chronic wounds. Int J Biol Macromol. 2019;132:97–108.
Yeh MK, Cheng KM, Hu CS, Huang YC, Young JJ. Novel protein-loaded chondroitin sulfate-chitosan nanoparticles: preparation and characterization. Acta Biomater. 2011;7:3804–12.
Liu ZG, Jiao YP, Liu FN, Zhang ZY. Heparin/chitosan nanoparticle carriers prepared by polyelectrolyte complexation. J Biomed Mater Res Part A. 2007;83:806–12.
de la Fuente M, Seijo B, Alonso M. Bioadhesive hyaluronan–chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue. Gene Ther. 2008;15:668–76.
Zhang L, Jin Y, Liu H, Du Y. Structure and control release of chitosan/carboxymethyl cellulose microcapsules. J Appl Polym Sci. 2001;82:584–92.
Wu D, Delair T. Stabilization of chitosan/hyaluronan colloidal polyelectrolyte complexes in physiological conditions. Carbohydr Polym. 2015;119:149–58.
Iijima K, Tsuji Y, Kuriki I, Kakimoto A, Nikaido Y, Ninomiya R, et al. Control of cell adhesion and proliferation utilizing polysaccharide composite film scaffolds. Colloids Surf B. 2017;160:228–37.
Yamazaki M, Iijima K. Fabrication and characterization of polysaccharide composite films from polyion complex particles. Polymers 2020;12:435.
Hansson AD, Francesco T, Falson F, Rousselle P, Jordan O, Borchard G. Preparation and evaluation of nanoparticles for directed tissue engineering. Int J Pharm. 2012;439:73–80.
Oosawa F. Polyeletrolytes. New York: M. Dekker; 1971.
Drogoz A, David L, Rochas C, Domard A, Delair T. Polyelectrolyte complexes from polysaccharides: formation and stoichiometry monitoring. Langmuir. 2007;23:10950–58.
Kulkarni AD, Vanjari YH, Sancheti KH, Patel HM, Belgamwar VS, Surana SJ, et al. Polyelectrolyte complexes: mechanisms, critical experimental aspects, and applications. Artif Cells Nanomed Biotechnol. 2016;44:1615–25.
Delair T. Colloidal polyelectrolyte complexes of chitosan and dextran sulfate towards versatile nanocarriers of bioactive molecules. Eur J Pharm Biopharm. 2011;78:10–8.
Shinoda K, Nakajima A. Complex formation of heparin or sulfated cellulose with glycol chitosan. Bull Inst Chem Res Kyoto Univ. 1975;53:392–9.
Shinoda K, Nakajima A. Complex formation of hyaluronic acid or chondroitin sulfate with glycol chitosan. Bull Inst Chem Res Kyoto Univ. 1975;53:400–8.
Adcock SA, McCammon JA. Molecular dynamics: survey of methods for simulating the activity of proteins. Chem Rev. 2006;106:1589–615.
Shen JW, Li J, Zhao Z, Zhang L, Peng G, Liang L. Molecular dynamics study on the mechanism of polynucleotide encapsulation by chitosan. Sci Rep. 2017;7:5050.
Zhao J, Xing T, Li Q, Chen Y, Yao WS, Jin SH, et al. Preparation of chitosan and carboxymethylcellulose-based polyelectrolyte complex hydrogel via SD-A-SGT method and its adsorption of anionic and cationic dye. J Appl Polym Sci. 2020;137:e48980.
Kirschner KN, Yongye AB, Tschampel SM, González-Outeiriño J, Daniels CR, Foley BL, et al. GLYCAM06: a generalizable biomolecular force field. Carbohydr J Comput Chem. 2008;29:622–55.
Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012;4:17.
Mulloy B, Forster MJ, Jones C, Davies D. N.m.r. and molecular-modelling studies of the solution conformation of heparin. Biochem J. 1993;293:849–58.
Kowsaka K, Okajima K, Kamide K. Further study on the distribution of substituent group in cellulose acetate by 13C{1H}NMR analysis: assignment of carbonyl carbon oeaks. Polym J. 1986;18:843–49.
Bernardi A, Faller R, Reith D, Kirschner KN. ACPYPE update for nonuniform 1–4 scale factors: conversion of the GLYCAM06 force field from AMBER to GROMACS. SoftwareX. 2019;10:100241.
Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1–2:19–25.
Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79:926–35.
Salomon-Ferrer R, Case DA, Walker RC. An overview of the Amber biomolecular simulation package. WIREs Comput Mol Sci. 2013;3:198–210.
Hess B, Bekker H, Berendsen HJ, Fraaije JG. LINCS: A linear constraint solver for molecular simulations. J Comput Chem. 1997;18:1463–72.
Darden T, York D, Pedersen L. Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. J Chem Phys. 1993;98:10089–92.
Bussi G, Donadio D, Parrinello M. Canonical sampling through velocity rescaling. J Chem Phys. 2007;126:14101.
Parrinello M, Rahman A. Crystal structure and pair potentials: a molecular-dynamics study. Phys Rev Lett. 1980;45:1196.
Fletcher R, Powell MA. A rapidly convergent descent method for minimization. J Comput. 1963;6:163–68.
The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.
Michaels AS. Polyelectrolyte complexes, Ind Eng Chem. 1965;57:32–40.
Popat K. Nanotechnology in tissue engineering and regenerative medicine. 1st ed. Boca Raton: CRC Press; 2010.
Franca EF, Freitas LC, Lins RD. Chitosan molecular structure as a function of N-acetylation. Biopolymers 2011;95:448–60.
Borca CH, Arango CA. Molecular dynamics of a water-absorbent nanoscale material based on chitosan. J Phys Chem B. 2016;120:3754–64.
Nagarajan B, Sankaranarayanan NV, Desai UR. Perspective on computational simulations of glycosaminoglycans. Wires Comput Mol Sci. 2019;9:e1388.
Chen WB, Wang LF, Chen JS, Fan SY. Characterization of polyelectrolyte complexes between chondroitin sulfate and chitosan in the solid state. J Biomed Mater Res A. 2005;75:128–37.
Hashizume M, Ohashi M, Kobayashi H, Tsuji Y, Iijima K. Free-standing polysaccharide composite films: Improved preparation and physical properties. Colloids Surf A. 2015;48:18–24.
Florczyk SJ, Wang K, Jana S, Wood DL, Sytsma SK, Sham J, et al. Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM. Biomaterials. 2013;34:10143–50.
Lamarque G, Lucas JM, Viton C, Domard A. Physicochemical behavior of homogeneous series of acetylated chitosans in aqueous solution: role of various structural parameters. Biomacromolecules. 2005;6:131–42.
Montembault A, Viton C, Domard A. Rheometric study of the gelation of chitosan in aqueous solution without cross-linking agent. Biomacromolecules. 2005;6:653–62.
Schatz C, Viton C, Delair T, Pichot C, Domard A. Typical physicochemical behaviors of chitosan in aqueous solution. Biomacromolecules. 2003;4:641–8.
Feng Y, Li J, Wang B, Tian X, Chen K, Zeng J, et al. Novel nanofibrillated cellulose/chitin whisker hybrid nanocomposites and their use for mechanical performance enhancements. Bioresources. 2018;13:3030–44.
Park JJ, Luo X, Yi H, Valentine TM, Payne GF, Bentley WE, et al. Chitosan-mediated in situ biomolecule assembly in completely packaged microfluidic devices. Lab Chip. 2006;6:1315–21.
Hashizume M, Murata Y, Iijima K, Shibata T. Drug loading and release behaviors of freestanding polysaccharide composite films. Polym J. 2016;48:545–50.
Acknowledgements
This research was partially supported by Leave a Nest grant IKEDA SCIENTIFIC award.
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Conceptualization: M. Yamazaki and K. Iijima; methodology: M. Yamazaki, M. Yabe, and K. Iijima; investigation: M. Yamazaki and M. Yabe; writing—original draft preparation: M. Yamazaki; writing—review and editing: M. Yabe and K. Iijima; supervision and project administration: K. Iijima.
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Yamazaki, M., Yabe, M. & Iijima, K. Analysis of the formation mechanism of polyion complexes of polysaccharides by molecular dynamics simulation with oligosaccharides. Polym J 54, 345–354 (2022). https://doi.org/10.1038/s41428-021-00602-y
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DOI: https://doi.org/10.1038/s41428-021-00602-y
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