Probing the protein corona around charged macromolecules: interpretation of isothermal titration calorimetry by binding models and computer simulations

Abstract

Isothermal titration calorimetry (ITC) is a widely used tool to experimentally probe the heat signal of the formation of the protein corona around macromolecules or nanoparticles. If an appropriate binding model is applied to the ITC data, the heat of binding and the binding stoichiometry as well as the binding affinity per protein can be quantified and interpreted. However, the binding of the protein to the macromolecule is governed by complex microscopic interactions. In particular, due to the steric and electrostatic protein–protein interactions within the corona as well as cooperative, charge renormalization effects of the total complex, the application of standard (e.g., Langmuir) binding models is questionable and the development of more appropriate binding models is very challenging. Here, we discuss recent developments in the interpretation of the Langmuir model applied to ITC data of protein corona formation, exemplified for the well-defined case of lysozyme coating highly charged dendritic polyglycerol sulfate (dPGS), and demonstrate that meaningful data can be extracted from the fits if properly analyzed. As we show, this is particular useful for the interpretation of ITC data by molecular computer simulations where binding affinities can be calculated but it is often not clear how to consistently compare them with the ITC data. Moreover, we discuss the connection of Langmuir models to continuum binding models (where no discrete binding sites have to be assumed) and their possible extensions toward the inclusion of leading order cooperative electrostatic effects.

Combined first-principles statistical mechanics approach to sulfur structure in organic cathode hosts for polymer based lithium–sulfur (Li–S) batteries

“…where the brackets denote the concentrations of reactants and products, 40 and v 0 = l mol À1 is the standard binding volume. [41][42][43] Note that the binding fractions of the concentrations of products and reactants in eqn ( 9) and ( 10) have the dimension of volume nÀ2 . Hence, we have to divide by the volume factor v nÀ2 0 to define the dimensionless equilibrium constants K n .…”

Molecular Modeling of Protein Corona Formation and Its Interactions with Nanoparticles and Cell Membranes for Nanomedicine Applications

“…Derakhshankhah et al’s simulations showed the non-cooperative binding between FG and zeolite nanoparticles via hydrogen bonds and electrostatic interactions of D-domain of FG [ 52 ]. Xu and Dzubiella calculated the binding free energies of lysozyme that was adsorbed onto the highly charged dendritic polyglycerol sulfate and derived the concept of a coverage-dependent binding affinity in the Langmuir model [ 53 ]. Sanchez-Guzman et al simulated oxyhemoglobin interacting with silica surfaces at pH 7 and pH 9 under different temperatures of 295 K, 322 K, 353 K, and 400 K, showing the dependence of the binding strength and structure on temperature and pH conditions [ 54 ].…”

Electrostatic reaction inhibition in nanoparticle catalysis

“…where V0 is the effective binding volume per binding site in the Langmuir picture. [59][60][61][62] The Langmuir binding volume V0 is a function of βεs and we calculate it for each adsorption energy by fitting the binding of neutral reactants to the one-component Langmuir isotherm (see the Supporting Information). For βεs = 1, V0 is well approximated by the shell volume divided by the saturation binding number, i.e., V0 = Vs/Nmax = 0.0288 nm 3 , i.e., as could be expected from the average available volume per particle if all Nmax 'sites' are occupied.…”

“…The V0 can be easily translated to the standard volume l/mol to refer to the standard energy of binding in experiments. [59][60][61] Furthermore, U is the surface (binding) energy experienced by the reactants…”