How protonation modulates the interaction between proteins and pH-responsive hydrogel films

Gabriel S. Longo*, Néstor A. Pérez-Chávez, Igal Szleifer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


Hydrogels of pH-responsive polymers are promising candidates for the design of functional biomaterials. In this context, understanding the complexity of the interaction between these materials and proteins is essential. A recently developed molecular-level equilibrium theory for protein adsorption on hydrogels of cross-linked polyacid chains allows for modeling size, shape, charge distribution, protonation state and conformational degrees of freedom of all chemical species in the system; proteins are described using a coarse-grained model of their crystallographic structure. This review summarizes our recent studies, which have focused on understanding how the interaction between proteins and pH-responsive hydrogel films depends on the pH and salt concentration, both in single protein solutions and mixtures. In particular, we discuss the key role that protonation plays in mediating the polymer-protein electrostatic attractions that drive adsorption. Deprotonation of the polyacid network modifies the nano-environment inside the hydrogel; the local pH drops inside the film. In single protein solutions, protonation of amino acid residues in this lower-pH environment favors adsorption to the hydrogel. Upon adsorption, the net charge of the protein can be several units more positive than in the solution. The various amino acids protonate differently, in a non-trivial way, which gives flexibility to the protein to enhance its positive charge and favor adsorption under a wide range of conditions. In binary and ternary protein solutions, amino acid protonation is the decisive factor for selective adsorption under certain conditions. We show that the polymer network composition and the solution pH can be used to separate and localize proteins within nanometer-sized regions.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalCurrent Opinion in Colloid and Interface Science
StatePublished - Jun 2019


  • Acid-base equilibrium
  • Protein adsorption
  • Protonation
  • pH-responsive hydrogels

ASJC Scopus subject areas

  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Polymers and Plastics
  • Colloid and Surface Chemistry


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