Charged polymer interactions govern biological and technological processes by altering the structure and dynamics of surrounding water. Studying these interactions across a broad concentration range is challenging, particularly at submicromolar levels where traditional methods lack sensitivity or molecular resolution. Here, we investigate interactions between hyaluronan (HA), a biologically and technologically relevant polymer, and model oligopeptides-nonaarginine, nonalysine, and nonaglycine. By combining angle-resolved second harmonic scattering (AR-SHS), dynamic light scattering, nuclear magnetic resonance, and all-atom molecular dynamics simulations, we resolve the molecular-scale mechanisms and structure of HA-peptide interactions. Our findings reveal selective, multivalent binding between HA and cationic peptides, inducing solvent and solute restructuring and nanoscale clustering. Simulations provide atomic-level insight, elucidating the transient nature of the interactions and highlighting the distinctive behavior of arginine-rich peptides. Our approach, integrating AR-SHS with simulations and routine techniques, offers molecular insights into polymer mixtures and a foundation for future studies of dynamic supramolecular systems in soft materials.

BioTechMed Center Gdańsk University of Technology Gdańsk Poland

Central European Institute of Technology Masaryk University Brno Czech Republic

Faculty of Chemistry Gdańsk University of Technology Gdańsk Poland

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Prague Czech Republic

Laboratory for fundamental BioPhotonics CH 1015 Lausanne Switzerland

National Centre for Biomolecular Research Faculty of Science Masaryk University Brno Czech Republic

Zobrazit více v PubMed

Jeon, S., Haynie, T., Chung, S. & Callmann, C. E. Bioinspired, carbohydrate-containing polymers efficiently and reversibly sequester heavy metals. PubMed DOI PMC

Zhang, X., Wang, J., Jin, H., Wang, S. & Song, W. Bioinspired supramolecular lubricating hydrogel induced by shear force. PubMed DOI

Toole, B. P. Hyaluronan: From extracellular glue to pericellular cue. PubMed DOI

Whitaker, D. & Powner, M. W. On the aqueous origins of the condensation polymers of life. PubMed DOI

Huang, G. & Huang, H. Application of hyaluronic acid as carriers in drug delivery. PubMed DOI PMC

Roget, S. A., Piskulich, Z. A., Thompson, W. H. & Fayer, M. D. Identical water dynamics in acrylamide hydrogels, polymers, and monomers in solution: Ultrafast ir spectroscopy and molecular dynamics simulations. PubMed DOI

Ramani, N. et al. Leveraging protein-ligand and DNA interactions to control hydrogel mechanics. PubMed DOI PMC

Rijns, L., Baker, M. B. & Dankers, P. Y. Using chemistry to recreate the complexity of the extracellular matrix: Guidelines for supramolecular hydrogel-cell interactions. PubMed PMC

Lin, W., Liu, Z., Kampf, N. & Klein, J. The role of hyaluronic acid in cartilage boundary lubrication. PubMed DOI PMC

Liu, Z. et al. Effects of hyaluronan molecular weight on the lubrication of cartilage-emulating boundary layers. PubMed DOI PMC

Van Oosten, A. S. & Janmey, P. A. Extremely charged and incredibly soft: Physical characterization of the pericellular matrix. PubMed DOI PMC

Cowman, M. K., Lee, H. G., Schwertfeger, K. L., McCarthy, J. B. & Turley, E. A. The content and size of hyaluronan in biological fluids and tissues. PubMed DOI PMC

Hintze, V., Schnabelrauch, M. & Rother, S. Chemical modification of hyaluronan and their biomedical applications. PubMed DOI PMC

Salih, A. R. C. et al. Hyaluronic acid: comprehensive review of a multifunctional biopolymer. DOI

Hou, X. et al. Recent advances in hyaluronic acid-based nanomedicines: Preparation and application in cancer therapy. PubMed DOI

Kale, N. R., Dutta, D., Carstens, W., Mallik, S. & Quadir, M. Functional applications of polyarginine-hyaluronic acid-based electrostatic complexes. PubMed DOI PMC

Chu, C. K. et al. Chemical tuning of fibers drawn from extensible hyaluronic acid networks. PubMed DOI PMC

Cai, P. C. et al. Rheological characterization and theoretical modeling establish molecular design rules for tailored dynamically associating polymers. PubMed DOI PMC

Highley, C. B., Prestwich, G. D. & Burdick, J. A. Recent advances in hyaluronic acid hydrogels for biomedical applications. PubMed DOI

Larrañeta, E. et al. Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications. PubMed DOI PMC

Yuan, Y., Shi, Y., Banerjee, J., Sadeghpour, A. & Azevedo, H. S. Structuring supramolecular hyaluronan hydrogels via peptide self-assembly for modulating the cell microenvironment. PubMed DOI PMC

Hennink, W. E. & van Nostrum, C. F. Novel crosslinking methods to design hydrogels. PubMed DOI

Pruksawan, S. et al. Enhancing hydrogel toughness by uniform cross-linking using modified polyhedral oligomeric silsesquioxane. DOI

Hunger, J., Bernecker, A., Bakker, H. J., Bonn, M. & Richter, R. P. Hydration dynamics of hyaluronan and dextran. PubMed DOI PMC

Giubertoni, G. et al. Molecular origin of the elastic state of aqueous hyaluronic acid. PubMed DOI PMC

van Dam, E. P., Giubertoni, G., Burla, F., Koenderink, G. H. & Bakker, H. J. Hyaluronan biopolymers release water upon pH-induced gelation. PubMed DOI

Karel, S. et al. Stabilization of hyaluronan-based materials by peptide conjugation and its use as a cell-seeded scaffold in tissue engineering. PubMed DOI

Varela-Aramburu, S. et al. Introducing hyaluronic acid into supramolecular polymers and hydrogels. PubMed DOI PMC

Duarte, D. et al. Bioadhesive hyaluronic acid-based hydrogels for spinal cord injury. PubMed DOI

Xu, X., Jha, A. K., Harrington, D. A., Farach-Carson, M. C. & Jia, X. Hyaluronic acid-based hydrogels: From a natural polysaccharide to complex networks. PubMed DOI PMC

Luo, Y. et al. From crosslinking strategies to biomedical applications of hyaluronic acid-based hydrogels: A review. PubMed DOI

Zimmermann, R., Werner, C. & Sterling, J. Exploring structure-property relationships of GAGs to tailor ECM-mimicking hydrogels. PubMed DOI PMC

Tavianatou, A. G. et al. Hyaluronan: Molecular size-dependent signaling and biological functions in inflammation and cancer. PubMed DOI

Garantziotis, S. & Savani, R. C. Hyaluronan biology: A complex balancing act of structure, function, location and context. PubMed DOI PMC

Vallet, S. D., Berthollier, C. & Ricard-Blum, S. The glycosaminoglycan interactome 2.0. PubMed DOI

Vuorio, J., Vattulainen, I. & Martinez-Seara, H. Atomistic fingerprint of hyaluronan–CD44 binding. PubMed DOI PMC

Hong, Y. et al. Hydrophobicity of arginine leads to reentrant liquid-liquid phase separation behaviors of arginine-rich proteins. PubMed DOI PMC

Oyarzun-Ampuero, F. A., Goycoolea, F. M., Torres, D. & Alonso, M. J. A new drug nanocarrier consisting of polyarginine and hyaluronic acid. PubMed DOI

Bridges, C. A. et al. The interplay between endothelial glycocalyx maturity and both the toxicity and intracellular uptake of charged nanoparticles. PubMed DOI

Biriukov, D. et al. The Origins of Arginine “Magic”: Guanidinium Like-Charge Ion Pairing and Oligoarginine Aggregation in Water by NMR, Cryoelectron Microscopy, and Molecular Dynamics Simulations. DOI

Villamizar-Sarmiento, M. G. et al. Ionic nanocomplexes of hyaluronic acid and polyarginine to form solid materials: A green methodology to obtain sponges with biomedical potential. PubMed DOI PMC

Matha, K. et al. Bioinspired hyaluronic acid and polyarginine nanoparticles for dachpt delivery. PubMed DOI

Urbaniak, T. et al. Layer-by-layer assembly of poly-l-lysine/hyaluronic acid protein reservoirs on poly(glycerol sebacate) surfaces. PubMed DOI

Khademhosseini, A. et al. Layer-by-layer deposition of hyaluronic acid and poly-l-lysine for patterned cell co-cultures. PubMed DOI

Le, H. V., Dulong, V., Picton, L. & Le Cerf, D. Thermoresponsive nanogels based on polyelectrolyte complexes between polycations and functionalized hyaluronic acid. PubMed DOI

Pan, W. et al. Core-corona structure formed by hyaluronic acid and poly(l-lysine) via kinetic path. DOI

Tang, S., Li, W., Zhu, Y., Hu, Q. & Wang, Y. Tat-conjugated hyaluronic acid enveloping polyplexes with facilitated nuclear entry and improved transfection. DOI

Quan, H. et al. Hyaluronic acid-decorated carborane-tat conjugation nanomicelles: A potential boron agent with enhanced selectivity of tumor cellular uptake. PubMed DOI

Yamada, Y., Hashida, M. & Harashima, H. Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in cd44 positive- and cd44 negative-cells. PubMed DOI

Bigo-Simon, A. et al. Mechanistic insights into hyaluronic acid induced peptide nanofiber organization in supramolecular hydrogels. PubMed DOI

Ziegler, A. & Seelig, J. Binding and clustering of glycosaminoglycans: A common property of mono- and multivalent cell-penetrating compounds. PubMed DOI PMC

Riopedre-Fernandez, M., Biriukov, D., Dračínský, M. & Martinez-Seara, H. Hyaluronan-arginine enhanced and dynamic interaction emerges from distinctive molecular signature due to electrostatics and side-chain specificity. PubMed DOI

Wolny, P. M. et al. Analysis of CD44-hyaluronan interactions in an artificial membrane system: Insights into the distinct binding properties of high and low molecular weight hyaluronan. PubMed DOI PMC

Jiang, L. et al. Molecular weight impact on the mechanical forces between hyaluronan and its receptor. PubMed DOI

Jugl, A. & Pekař, M. Hyaluronan-arginine interactions-an ultrasound and ITC study. PubMed DOI PMC

Kulik, N., Minofar, B., Jugl, A. & Pekař, M. Computational study of complex formation between hyaluronan polymers and polyarginine peptides at various ratios. PubMed DOI PMC

Chen, Y. et al. Electrolytes induce long-range orientational order and free energy changes in the H-bond network of bulk water. PubMed DOI PMC

Marchioro, A. et al. Surface characterization of colloidal silica nanoparticles by second harmonic scattering: Quantifying the surface potential and interfacial water order. PubMed DOI PMC

Dedic, J., Okur, H. I. & Roke, S. Polyelectrolytes induce water-water correlations that result in dramatic viscosity changes and nuclear quantum effects. PubMed DOI PMC

Dedic, J., Okur, H. I. & Roke, S. Hyaluronan orders water molecules in its nanoscale extended hydration shells. PubMed DOI PMC

Bischoff, M., Biriukov, D., Předota, M. & Marchioro, A. Second harmonic scattering reveals ion-specific effects at the SiO PubMed DOI PMC

Nencini, R. et al. Effective inclusion of electronic polarization improves the description of electrostatic interactions: The prosECCo75 biomolecular force field. PubMed DOI PMC

Riopedre-Fernandez, M., Kostal, V., Martinek, T., Martinez-Seara, H. & Biriukov, D. Developing and benchmarking sulfate and sulfamate force field parameters via ab initio molecular dynamics simulations to accurately model glycosaminoglycan electrostatic interactions. PubMed DOI PMC

Lay, W. K., Miller, M. S. & Elcock, A. H. Optimizing solute-solute interactions in the GLYCAM06 and CHARMM36 carbohydrate force fields using osmotic pressure measurements. PubMed DOI PMC

Lay, W. K., Miller, M. S. & Elcock, A. H. Reparameterization of solute-solute interactions for amino acid-sugar systems using isopiestic osmotic pressure molecular dynamics simulations. PubMed DOI PMC

Beer, A. G. F. D., Roke, S. & Dadap, J. I. Theory of optical second-harmonic and sum-frequency scattering from arbitrarily shaped particles. DOI

Jen, S. H., Gonella, G. & Dai, H. L. The effect of particle size in second harmonic generation from the surface of spherical colloidal particles. i: experimental observations. PubMed DOI

Chu, B., Marchioro, A. & Roke, S. Size dependence of second-harmonic scattering from nanoparticles: Disentangling surface and electrostatic contributions. PubMed DOI

Allolio, C. et al. Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore. PubMed DOI PMC

Willcott, M. R. MestRe nova. DOI

Lee, J. et al. CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field. PubMed DOI PMC

Schrödinger, LLC. The PyMOL molecular graphics system, version 1.8 (2015).

Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. DOI

Durell, S. R., Brooks, B. R. & Ben-Naim, A. Solvent-induced forces between two hydrophilic groups. DOI

Abraham, M. J. et al. Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. DOI

Essmann, U. et al. A smooth particle mesh Ewald method. DOI

Steinbach, P. J. & Brooks, B. R. New spherical-cutoff methods for long-range forces in macromolecular simulation. DOI

Bussi, G., Donadio, D. & Parrinello, M. Canonical sampling through velocity rescaling. PubMed DOI

Bernetti, M. & Bussi, G. Pressure control using stochastic cell rescaling. PubMed DOI

Miyamoto, S. & Kollman, P. A. Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models. DOI

Hess, B. P-LINCS: A parallel linear constraint solver for molecular simulation. PubMed DOI

Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: A toolkit for the analysis of molecular dynamics simulations. PubMed DOI PMC

Ivanović, M. T. & Best, R. B. All-atom simulations of biomolecular condensates. PubMed PMC