Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Electrostatic control of protein adsorption onto negatively charged crystalline cello-oligosaccharide assemblies

Abstract

Protein adsorption onto surfaces is a critical process in biomaterial science, influencing subsequent biological responses. Understanding this phenomenon is key to designing materials with controlled interactions for biomedical applications. Here, we report controllable protein adsorption onto crystalline lamellar assemblies of carboxylated cello-oligosaccharides synthesized via cellodextrin phosphorylase-catalyzed oligomerization. These assemblies, featuring a terminal carboxy group linked by alkyl chains, possessed a negative surface charge, the magnitude of which depended on alkyl linker length, pH, and ionic strength, as confirmed by zeta potential measurements. Under varying pH and ionic strength conditions, we observed significant adsorption of basic proteins, which increased with longer alkyl linkers and lower ionic strength. Although acidic protein adsorption at acidic pH was minimal under high ionic strength, we notably found that acidic proteins were adsorbed onto negatively charged assemblies under low ionic strength. Our results demonstrate that electrostatic interactions primarily govern protein adsorption on these assemblies, enabling controllable protein adsorption through the adjustment of their surface properties and solution conditions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ogoshi T. Supramolecular assemblies and polymer recognition based on polygonal and pillar-shaped macrocycles “pillar[n]arenes. Polym J. 2023;55:1247–60.

    Article  CAS  Google Scholar 

  2. Masuda T. Design of functional soft interfaces with precise control of the polymer architecture. Polym J. 2024;56:643–52.

    Article  CAS  Google Scholar 

  3. Uchida N. Design of supramolecular nanosheets for drug delivery applications. Polym J. 2023;55:829–36.

    Article  CAS  Google Scholar 

  4. Inaba H. Construction of functional microtubules and artificial motile systems based on peptide design. Polym J. 2023;55:1261–74.

    Article  CAS  Google Scholar 

  5. Murai K. Development of peptide–inorganic hybrid materials based on biomineralization and their functional design based on structural controls. Polym J. 2023;55:817–27.

    Article  CAS  Google Scholar 

  6. Nishimura S, Tanaka M. The intermediate water concept for pioneering polymeric biomaterials: a review and update. Bull Chem Soc Jpn. 2023;96:1052–70.

    Article  CAS  Google Scholar 

  7. Hattori T. Colloidal titration: from the perspective of stability constants between oppositely charged polyelectrolytes. Bull Chem Soc Jpn. 2024;97:uoae044.

    Article  CAS  Google Scholar 

  8. Roy B, Govindaraju T. Enzyme-mimetic catalyst architectures: the role of second coordination sphere in catalytic activity. Bull Chem Soc Jpn. 2024;97:bcsj.20230224.

    Article  CAS  Google Scholar 

  9. Miyamoto T, Numata K. Advancing biomolecule delivery in plants: harnessing synthetic nanocarriers to overcome multiscale barriers for cutting-edge plant bioengineering. Bull Chem Soc Jpn. 2023;96:1026–44.

    Article  CAS  Google Scholar 

  10. Nilsson PH, Ekdahl KN, Magnusson PU, Qu H, Iwata H, Ricklin D, et al. Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating. Biomaterials. 2013;34:985–94.

    Article  PubMed  CAS  Google Scholar 

  11. Sivaraman B, Latour RA. The relationship between platelet adhesion on surfaces and the structure versus the amount of adsorbed fibrinogen. Biomaterials. 2010;31:832–9.

    Article  PubMed  CAS  Google Scholar 

  12. Wei Q, Becherer T, Angioletti-Uberti S, Dzubiella J, Wischke C, Neffe AT, et al. Protein interactions with polymer coatings and biomaterials. Angew Chem Int Ed. 2014;53:8004–31.

    Article  CAS  Google Scholar 

  13. Firkowska-Boden I, Zhang X, Jandt KD. Controlling protein adsorption through nanostructured polymeric surfaces. Adv Health Mater. 2018;7:1700995.

    Article  Google Scholar 

  14. Li J, Han Q, Zhang Y, Zhang W, Dong M, Besenbacher F, et al. Optical regulation of protein adsorption and cell adhesion by photoresponsive GaN nanowires. ACS Appl Mater Interfaces. 2013;5:9816–22.

    Article  PubMed  CAS  Google Scholar 

  15. Tang J, Qiu Y, Li Z. Osteopontin facilitated dental pulp cell adhesion and differentiation: a laboratory investigation. ACS Appl Bio Mater. 2025;8:1320–9.

    Article  PubMed  CAS  Google Scholar 

  16. Kubiak-Ossowska K, Tokarczyk K, Jachimska B, Mulheran PA. Bovine serum albumin adsorption at a silica surface explored by simulation and experiment. J Phys Chem B. 2017;121:3975–86.

    Article  PubMed  CAS  Google Scholar 

  17. Kubiak-Ossowska K, Mulheran PA. Mechanism of hen egg white lysozyme adsorption on a charged solid surface. Langmuir. 2010;26:15954–65.

    Article  PubMed  CAS  Google Scholar 

  18. Miyagawa A, Hagiya K, Nagatomo S, Nakatani K. Protein adsorption on carboxy-functionalized microparticles revealed by zeta potential and absorption spectroscopy measurements. Bull Chem Soc Jpn. 2023;96:759–65.

    Article  CAS  Google Scholar 

  19. Thiramanas R, Wongngam Y, Supanakorn G, Polpanich D. BSA adsorption on titanium dioxide nanoparticle surfaces for controlling their cellular uptake in skin cells. ACS Appl Bio Mater. 2024;7:1713–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Moerz ST, Huber P. pH-dependent selective protein adsorption into mesoporous silica. J Phys Chem C. 2015;119:27072–9.

    Article  CAS  Google Scholar 

  21. Meissner J, Prause A, Bharti B, Findenegg GH. Characterization of protein adsorption onto silica nanoparticles: influence of pH and ionic strength. Colloid Polym Sci. 2015;293:3381–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Kubiak-Ossowska K, Jachimska B, Mulheran PA. How negatively charged proteins adsorb to negatively charged surfaces: a molecular dynamics study of BSA adsorption on silica. J Phys Chem B. 2016;120:10463–8.

    Article  PubMed  CAS  Google Scholar 

  23. Salgın S, Takaç S, Özdamar TH. Adsorption of bovine serum albumin on polyether sulfone ultrafiltration membranes: determination of interfacial interaction energy and effective diffusion coefficient. J Membr Sci. 2006;278:251–60.

    Article  Google Scholar 

  24. Yu Q, Chen H, Zhang Y, Yuan L, Zhao T, Li X, et al. pH-reversible, high-capacity binding of proteins on a substrate with nanostructure. Langmuir. 2010;26:17812–5.

    Article  PubMed  CAS  Google Scholar 

  25. Hober S, Nord K, Linhult M. Protein A chromatography for antibody purification. J Chromatogr B. 2007;848:40–7.

    Article  CAS  Google Scholar 

  26. Jung Y-D, Khan M, Park S-Y. Fabrication of temperature- and pH-sensitive liquid-crystal droplets with PNIPAM-b-LCP and SDS coatings by microfluidics. J Mater Chem B. 2014;2:4922–8.

    Article  PubMed  CAS  Google Scholar 

  27. Klemm D, Heublein B, Fink H-P, Bohn A. Cellulose: fascinating biopolymer and sustainable raw material. Angew Chem Int Ed. 2005;44:3358–93.

    Article  CAS  Google Scholar 

  28. Li T, Chen C, Brozena AH, Zhu JY, Xu L, Driemeier C, et al. Developing fibrillated cellulose as a sustainable technological material. Nature. 2021;590:47–56.

    Article  PubMed  CAS  Google Scholar 

  29. Heise K, Kontturi E, Allahverdiyeva Y, Tammelin T, Linder MB, Nonappa, et al. Nanocellulose: recent fundamental advances and emerging biological and biomimicking applications. Adv Mater. 2021;33:2004349.

    Article  PubMed  CAS  Google Scholar 

  30. Klemm D, Kramer F, Moritz S, Lindström T, Ankerfors M, Gray D, et al. Nanocelluloses: a new family of nature-based materials. Angew Chem Int Ed. 2011;50:5438–66.

    Article  CAS  Google Scholar 

  31. Habibi Y, Lucia LA, Rojas OJ. Cellulose nanocrystals: chemistry, self-assembly, and applications. Chem Rev. 2010;110:3479–500.

    Article  PubMed  CAS  Google Scholar 

  32. Tardy BL, Mattos BD, Otoni CG, Beaumont M, Majoinen J, Kämäräinen T, et al. Deconstruction and reassembly of renewable polymers and biocolloids into next generation structured materials. Chem Rev. 2021;121:14088–188.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Moon RJ, Martini A, Nairn J, Simonsen J, Youngblood J. Cellulose nanomaterials review: structure, properties and nanocomposites. Chem Soc Rev. 2011;40:3941–94.

    Article  PubMed  CAS  Google Scholar 

  34. Barhoum A, Jeevanandam J, Rastogi A, Samyn P, Boluk Y, Dufresne A, et al. Plant celluloses, hemicelluloses, lignins, and volatile oils for the synthesis of nanoparticles and nanostructured materials. Nanoscale. 2020;12:22845–90.

    Article  PubMed  CAS  Google Scholar 

  35. Shi Y, Jiao H, Sun J, Lu X, Yu S, Cheng L, et al. Functionalization of nanocellulose applied with biological molecules for biomedical application: a review. Carbohydr Polym. 2022;285:119208.

    Article  PubMed  CAS  Google Scholar 

  36. Ong X-R, Chen AX, Li N, Yang YY, Luo H-K. Nanocellulose: recent advances toward biomedical applications. Small Sci. 2023;3:2200076.

    Article  PubMed  CAS  Google Scholar 

  37. Hata Y, Serizawa T. Nanoarchitectonics of cello-oligosaccharides: a route toward artificial nanocelluloses. Adv Colloid Interface Sci. 2025;336:103361.

    Article  PubMed  CAS  Google Scholar 

  38. Hiraishi M, Igarashi K, Kimura S, Wada M, Kitaoka M, Samejima M. Synthesis of highly ordered cellulose II in vitro using cellodextrin phosphorylase. Carbohydr Res. 2009;344:2468–73.

    Article  PubMed  CAS  Google Scholar 

  39. Sletten ET, Fittolani G, Hribernik N, Dal Colle MCS, Seeberger PH, Delbianco M. Phosphates as assisting groups in glycan synthesis. ACS Cent Sci. 2024;10:138–42.

    Article  PubMed  CAS  Google Scholar 

  40. Djalali S, Yadav N, Delbianco M. Towards glycan foldamers and programmable assemblies. Nat Rev Mater. 2024;9:190–201.

    Article  Google Scholar 

  41. Hata Y, Serizawa T. Self-assembly of cellulose for creating green materials with tailor-made nanostructures. J Mater Chem B. 2021;9:3944–66.

    Article  PubMed  CAS  Google Scholar 

  42. Hata Y, Serizawa T. Robust gels composed of self-assembled cello-oligosaccharide networks. Bull Chem Soc Jpn. 2021;94:2279–89.

    Article  CAS  Google Scholar 

  43. Serizawa T, Yamaguchi S, Sugiura K, Marten R, Yamamoto A, Hata Y, et al. Antibacterial synthetic nanocelluloses synergizing with a metal-chelating agent. ACS Appl Bio Mater. 2024;7:246–55.

    Article  PubMed  CAS  Google Scholar 

  44. Mizuuchi Y, Hata Y, Sawada T, Serizawa T. Surface-mediated self-assembly of click-reactive cello-oligosaccharides for fabricating functional nonwoven fabrics. Sci Technol Adv Mater. 2024;25:2311052.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Suehiro F, Hata Y, Sawada T, Serizawa T. Freeze-dryable, stable, and click-reactive nanoparticles composed of cello-oligosaccharides for biomolecular sensing. ACS Appl Bio Mater. 2024;7:4007–16.

    Article  PubMed  CAS  Google Scholar 

  46. Sugiura K, Sawada T, Hata Y, Tanaka H, Serizawa T. Distinguishing anti-PEG antibodies by specificity for the PEG terminus using nanoarchitectonics-based antibiofouling cello-oligosaccharide platforms. J Mater Chem B. 2024;12:650–7.

    Article  PubMed  CAS  Google Scholar 

  47. Sugiura K, Saito M, Sawada T, Tanaka H, Serizawa T. Cellodextrin phosphorylase-catalyzed single-process production and superior mechanical properties of organic–inorganic hybrid hydrogels composed of surface-carboxylated synthetic nanocelluloses and hydroxyapatite. ACS Sustain Chem Eng. 2022;10:13484–94.

    Article  CAS  Google Scholar 

  48. Nohara T, Sawada T, Tanaka H, Serizawa T. Templated synthesis of gold nanoparticles on surface-aminated 2D cellulose assemblies. Bull Chem Soc Jpn. 2019;92:982–8.

    Article  CAS  Google Scholar 

  49. Nohara T, Sawada T, Tanaka H, Serizawa T. Enzymatic synthesis and protein adsorption properties of crystalline nanoribbons composed of cellulose oligomer derivatives with primary amino groups. J Biomater Sci Polym Ed. 2017;28:925–38.

    Article  PubMed  CAS  Google Scholar 

  50. Serizawa T, Yamaguchi S, Amitani M, Ishii S, Tsuyuki H, Tanaka Y, et al. Alkyl chain length-dependent protein nonadsorption and adsorption properties of crystalline alkyl β-celluloside assemblies. Colloids Surf B. 2022;220:112898.

    Article  CAS  Google Scholar 

  51. Langan P, Nishiyama Y, Chanzy H. X-ray structure of mercerized cellulose II at 1 Å resolution. Biomacromolecules. 2001;2:410–6.

    Article  PubMed  CAS  Google Scholar 

  52. Lvov Y, Ariga K, Ichinose I, Kunitake T. Assembly of multicomponent protein films by means of electrostatic layer-by-layer adsorption. J Am Chem Soc. 1995;117:6117–23.

    Article  CAS  Google Scholar 

  53. Alves JEF, Lucena MLC, de Souza Lucena AE, das Merces AAD, de Azevedo RDS, Sousa GLS, et al. SMV. A simple method for obtaining human albumin and its use for in vitro interaction assays with indole-thiazole and indole-thiazolidinone derivatives. Int J Biol Macromol. 2021;192:126–37.

    Article  PubMed  CAS  Google Scholar 

  54. Serizawa T, Maeda T, Sawada T. Neutralization-induced self-assembly of cellulose oligomers into antibiofouling crystalline nanoribbon networks in complex mixtures. ACS Macro Lett. 2020;9:301–5.

    Article  PubMed  CAS  Google Scholar 

  55. Jiang X, Weise S, Hafner M, Röcker C, Zhang F, Parak WJ, et al. Quantitative analysis of the protein corona on FePt nanoparticles formed by transferrin binding. J R Soc Interface. 2009;7:S5–13.

    PubMed  PubMed Central  Google Scholar 

  56. Wangkam T, Yodmongkol S, Disrattakit J, Sutapun B, Amarit R, Somboonkaew A, et al. Adsorption of bovine serum albumin (BSA) on polystyrene (PS) and its acid copolymer. Curr Appl Phys. 2012;12:44–52.

    Article  Google Scholar 

  57. He XM, Carter DC. Atomic structure and chemistry of human serum albumin. Nature. 1992;358:209–15.

    Article  PubMed  CAS  Google Scholar 

  58. Reynolds EC, Wong A. Effect of adsorbed protein on hydroxyapatite zeta potential and Streptococcus mutans adherence. Infect Immun. 1983;39:1285–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Hanamura M, Sawada T, Serizawa T. In-paper self-assembly of cellulose oligomers for the preparation of all-cellulose functional paper. ACS Sustain Chem Eng. 2021;9:5684–92.

    Article  CAS  Google Scholar 

  60. Hata Y, Miyazaki H, Okamoto S, Serizawa T, Nakamura S. Nanospiked cellulose gauze that attracts bacteria with biomolecules for reducing bacterial load in burn wounds. Nano Lett. 2025;25:1177–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Wang Y, Nor YA, Song H, Yang YN, Xu C, Yu MH, et al. Small-sized and large-pore dendritic mesoporous silica nanoparticles enhance antimicrobial enzyme delivery. J Mater Chem B. 2016;4:2646–53.

    Article  PubMed  CAS  Google Scholar 

  62. Anastas PT, Rodriguez A, de Winter TM, Coish P, Zimmerman JB. A review of immobilization techniques to improve the stability and bioactivity of lysozyme. Green Chem Lett Rev. 2021;14:302–38.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Professor Toshiki Sawada (Institute of Science Tokyo) for his valuable contributions through helpful advice on the experiments and insightful discussions. The authors thank Professor Shingo Nakamura, Professor Hiromi Miyazaki, and Dr. Kazunori Morohoshi (National Defense Medical College Research Institute) for zeta potential measurements. We are grateful for the financial support to TS from a Grant-in-Aid for Scientific Research on Innovative Areas (Aquatic Functional Materials) (JP22H04528) from the Ministry of Education, Culture, Sports, Science and Technology, Japan and a Grant-in-Aid for Scientific Research (B) (JP24K01548) from the Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takeshi Serizawa.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sugiura, K., Matsunami, A., Hata, Y. et al. Electrostatic control of protein adsorption onto negatively charged crystalline cello-oligosaccharide assemblies. Polym J (2025). https://doi.org/10.1038/s41428-025-01104-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41428-025-01104-x

Search

Quick links