Abstract

The widespread interest in neutral, water-soluble polymers such as poly(ethylene glycol) (PEG) and poly(zwitterions) such as poly(sulfobetaine) (pSB) for biomedical applications is due to their widely assumed low protein binding. Here we demonstrate that pSB chains in solution can interact with proteins directly. Moreover, pSB can reduce the thermal stability and increase the protein folding cooperativity relative to proteins in buffer or in PEG solutions. Polymer-dependent changes in the tryptophan fluorescence spectra of three structurally-distinct proteins reveal that soluble, 100 kDa pSB interacts directly with all three proteins and changes both the local polarity near tryptophan residues and the protein conformation. Thermal denaturation studies show that the protein melting temperatures decrease by as much as ∼1.9 °C per weight percent of polymer and that protein folding cooperativity increases by as much as ∼130 J mol-1 K-1 per weight percent of polymer. The exact extent of the changes is protein-dependent, as some proteins exhibit increased stability, whereas others experience decreased stability at high soluble pSB concentrations. These results suggest that pSB is not universally protein-repellent and that its efficacy in biotechnological applications will depend on the specific proteins used.

Original languageEnglish (US)
Pages (from-to)3894-3901
Number of pages8
JournalBiomacromolecules
Volume19
Issue number9
DOIs
StatePublished - Sep 10 2018

Fingerprint

Proteins
Polymers
Polyethylene glycols
Protein folding
Tryptophan
sulfobetaine
Denaturation
Melting point
Conformations
Buffers
Thermodynamic stability
Fluorescence
Water

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Soluble Zwitterionic Poly(sulfobetaine) Destabilizes Proteins. / Kisley, Lydia; Serrano, Kali A.; Davis, Caitlin M.; Guin, Drishti; Murphy, Elizabeth A.; Gruebele, Martin H W; Leckband, Deborah E.

In: Biomacromolecules, Vol. 19, No. 9, 10.09.2018, p. 3894-3901.

Research output: Contribution to journalArticle

Kisley L, Serrano KA, Davis CM, Guin D, Murphy EA, Gruebele MHW et al. Soluble Zwitterionic Poly(sulfobetaine) Destabilizes Proteins. Biomacromolecules. 2018 Sep 10;19(9):3894-3901. https://doi.org/10.1021/acs.biomac.8b01120
Kisley, Lydia ; Serrano, Kali A. ; Davis, Caitlin M. ; Guin, Drishti ; Murphy, Elizabeth A. ; Gruebele, Martin H W ; Leckband, Deborah E. / Soluble Zwitterionic Poly(sulfobetaine) Destabilizes Proteins. In: Biomacromolecules. 2018 ; Vol. 19, No. 9. pp. 3894-3901.
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