Adsorption and protonation of peptides and proteins in pH responsive gels

Abstract

To describe the non-trivial features of the equilibrium protonation and physical adsorption of peptides/proteins in pH-responsive hydrogels, we summarize our recent theoretical work on the subject. In these systems, molecular confinement in nanometer-sized environments modifies the balance between chemical state, physical interactions and molecular organization, which results in a behavior that is qualitatively different from what is expected from assuming the bulk solution protonation. To enhance adsorption, the pH-dependent deprotonation curves of all amino acids of adsorbed proteins are adequately shifted and deformed, which depends, in a complex fashion, on the specific amino acid. This possibility of modifying different acid-base equilibriums gives the adsorbed protein degrees of freedom to regulate charge and enhance electrostatic attractions under a wide range of experimental conditions. Protein adsorption modifies the microenvironment inside the hydrogel, particularly the gel pH. As a result, the state of protonation of the network is different before and after adsorption. The physicochemical considerations described in this review can be useful in the design of functional materials involving protein adsorption.

Electrostatically Driven Protein Adsorption: Charge Patches versus Charge Regulation

“…7,10,11,[15][16][17] Such dependence of adsorption with ionic strength suggests that electrostatic interactions favor adsorption even for proteins with zero net charge or proteins with a charge of the same sign as that of the surface. Two mechanisms have been proposed to explain this result, the charge-regulation (CR) effect [18][19][20] and the charge-patches (CP) mechanism. 15,16,21 In the CR effect, the presence of the charged surface induces a charge of the opposite sign in the protein by displacing the acid-base chemical equilibria of its aminoacids, thus favoring adsorption.…”

Designing biopolymer microgels to encapsulate, protect and deliver bioactive components: Physicochemical aspects

“… Electrical properties: The change in surface potential (-potential) of the biopolymer molecules with pH should be known because this often influences their ability to form microgels, e.g., by cross-linking with oppositely charged mineral ions or biopolymer molecules [28]. Changes in the internal electrical properties of microgels (such as the charge density and sign) can also be used to control the retention and release of charged bioactive molecules [29]. Moreover, the -potential versus pH profile of the microgels themselves influences their aggregation stability by altering the electrostatic interactions between them [30], as well as their interactions with other charge species.…”

“…The electrical characteristics of the interior of microgel particles is also important for many applications, and is mainly determined by the linear charge density of the biopolymer molecules in the gel network, as well as any associated mineral ions [29].…”

“…Computer simulations show that the pH and ion distribution within the interior of a hydrogel matrix may be quite different from that of the surrounding aqueous phase, which alters the ionization of both the biopolymer molecules and bioactive agents [29,140]. For example, the pH inside a hydrogel matrix consisting of anionic biopolymers may be appreciably less than that of the surrounding aqueous phase.…”

“…The system reduces the magnitude of this repulsion by increasing the local proton concentration, thereby causing some of the anionic groups to become protonated and lose their charge. The magnitude of the difference in pH between the inside and outside of the biopolymer matrix increases with decreasing ionic strength and increasing biopolymer charge density [29]. This phenomenon may be utilized to retain charged bioactive molecules (such as proteins or peptides) inside microgels over a certain range of external pH conditions, but then release them under another set of pH conditions.…”