Sorption and Spatial Distribution of Protein Globules in Charged Hydrogel Particles

Abstract

We have theoretically studied the uptake of a non-uniformly charged biomolecule, suitable to represent a globular protein or a drug, by a charged hydrogel carrier in the presence of a 1:1 electrolyte. Based on the analysis of a physical interaction Hamiltonian including monopolar, dipolar and Born (self-energy) contributions derived from linear electrostatic theory of the unperturbed homogeneous hydrogel, we have identified five different sorption states of the system, from complete repulsion of the molecule to its full sorption deep inside the hydrogel, passing through meta-and stable surface adsorption states. The results are summarized in state diagrams that also explore the effects of varying the electrolyte concentration, the sign of the net electric charge of the biomolecule, and the role of including excluded-volume (steric) or hydrophobic biomolecule-hydrogel interactions. We show that the dipole moment of the biomolecule is a key parameter controlling the spatial distribution of the globules. In particular, biomolecules with a large dipole moment tend to be adsorbed at the external surface of the hydrogel, even if like-charged, whereas uniformly charged biomolecules tend to partition towards the internal core of an oppositely-charged hydrogel. Hydrophobic attraction shifts the states towards internal sorption of the biomolecule, whereas steric repulsion promotes surface adsorption for oppositely-charged biomolecules, or the total exclusion for likely-charged ones. Our results establish a guidance for the spatial partitioning of proteins and drugs in hydrogel carriers, tuneable by hydrogel charge, pH and salt concentration.

Nonequilibrium Uptake Kinetics of Molecular Cargo into Hollow Hydrogels Tuned by Electrosteric Interactions

“…3). 46,61 V elec represents the effective electrostatic interaction between the cosolute and the charge distribution of the hydrogel and the ions surrounding it. Neglecting high order multipolar contributions, V elec (r) can be expressed as the sum of a monopolar term, an attractive orientation-averaged dipolar term, and a Born solvation self-energy…”

“…For this purpose, a phenomenological effective pair potential, V eff (r), that combines electrostatic, osmotic and excluded-volume (steric) energetic contributions is deduced for the cosolute-hydrogel, interactions. 46 In our model, we consider the general situation of non-uniformly charged cosolutes (such as the case of heterogeneous reactants, ligands, small proteins, etc), and include the Born solvation attraction to account for the charge screening effects caused by the excess of counterions inside the charged hydrogel. We employ the resulting effective Hamiltonian to explore a wide spectrum of parameters, and summarize the results by means of state diagrams, where the final equilibrium states are classified into seven different categories: weak and strong exclusion/absorption of cosolute inside the hydrogel membrane, and metastable, weak and strong adsorption onto the surfaces of the hydrogel.…”

Theory, simulations and the design of functionalized nanoparticles for biomedical applications: A Soft Matter Perspective

“…109,110 In a similar way, the interaction between the polymer chain and proteins, as well as that of the grafting surface with both the polymer and the protein can also be included. 97 Within a mean-field approach, electrostatic interactions are usually introduced via a Poisson-Boltzmann description [111][112][113] or on a coarser level assuming local electroneutrality. 106 The inclusion of electrostatic interactions is quite important considering that under physiologically relevant Design of nanoparticles: A Soft Matter Perspective S Angioletti-Uberti conditions most proteins and various biocompatible polymers used in applications are charged.…”

“…113 These authors improved the model by solving the full Poisson-Boltzmann equations for the electrostatic potential within the system. Even more importantly, the effect of the charge distribution on the protein's surface was included, in contrast with all previous studies described here where a spherically distributed charge is assumed.…”

“…In these nanogels, electrostatic gradients are relevant only at the interface with the solution and decay exponentially away from it with a decay length equal to the salt-dependent Debye screening length. 113 Hence, dipoles favour adsorption at the interface rather than inside the gel. By looking at the competition of different terms and at the effective potential for adsorption arising, Adroher-Benítez et al were able to show that there exist various adsorption states, similar to what was described by Halperin and Kröger in polymer brushes.…”