BIOPHYSICAL THEORY AND MODELING |
Kinetics of Protein Adsorption and Desorption on Surfaces with Grafted Polymers
Fang Fang 1, Javier Satulovsky 2 and Igal Szleifer 1*
1 Purdue University
2 Washington University Medical School
* To whom correspondence should be addressed. E-mail: igal{at}purdue.edu.
Submitted on October 27, 2004
Revised on December 29, 2004
Accepted on 2 June 2005
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Abstract |
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The kinetics of protein adsorption are studied using a generalized diffusion approach which shows that the time determining step in the adsorption is the crossing of the kinetic barrier presented by the polymers and already adsorbed proteins. The potential of mean-force between the adsorbing protein and the polymer-protein surface changes as a function of time due to the deformation of the polymer layers as the proteins adsorb. Furthermore, the range and strength of the repulsive interaction felt by the approaching proteins increases with grafted polymer molecular weight and surface coverage. The effect of molecular weight on the kinetics is very complex and different than its role on the equilibrium adsorption isotherms. The very large kinetic barriers make the time scale for the adsorption process very long and the computational effort increases with time, thus, an approximate kinetic approach is developed. The kinetic theory is based on the knowledge that the time determining step is crossing the potential of mean-force barrier. Kinetic equations for two states (adsorbed and bulk) are written where the kinetic coefficients are the product of the Boltzmann factor for the free energy of adsorption (desorption) multiplied by a preexponential factor determined from a Kramer's like theory. The predictions from the kinetic approach are in excellent quantitative agreement with the full diffusion equation solutions demonstrating that the two most important physical process are the crossing of the barrier and the changes in the barrier with time due to the deformation of the polymer layer as the proteins adsorb/desorb. The kinetic coefficients can be calculated a priori allowing for systematic calculations over very long time scales. It is found that in many cases where the equilibrium adsorption shows a finite value the kinetics of the process is so slow that experimental system will show no adsorption. This effect is particularly important at high grafted polymer surface coverage. The construction of guidelines for molecular weight/surface coverage necessary for kinetic prevention of protein adsorption in a desired time scale is shown. The time dependent desorption is also studied by modeling how adsorbed proteins leave the surface when in contact with a pure water solution. It is found that the kinetics of desorption are very slow and depend in a non-monotonic way in the polymer chain length. When the polymer layer thickness is shorter than the size of the protein, increasing polymer chain length, at fixed surface coverage, makes the desorption process faster. For polymer layers with thickness larger than the protein size, increases molecular weight results in a longer time for desorption. This is due to the grafted polymers trapping the adsorbed proteins and slowing down the desorption process. These results offer a possible explanation to some experimental data on adsorption. Limitations and extension of the developed approaches for practical applications are discussed.
Key Words:
grafted polymer layers, kinetic vs thermodynamic control, molecular theory, non-fouling surfaces, protein adsorption and desorption, steric repulsion
