Kinetics of Protein Adsorption and Desorption on Surfaces with Grafted Polymers

Abstract

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 timescale 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 Kramers-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 processes 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 timescales. It is found that, in many cases where the equilibrium adsorption shows a finite value, the kinetics of the process is so slow that the 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 timescale 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 nonmonotonic 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 in 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.

Controlled release of proteins from polymer-modified surfaces

“…The range of validity of this description of the kinetics of adsorption has been discussed elsewhere (15,19), and it is valid for all of the cases of interest in here. The most important information that describes the time-dependent adsorption is in the rate coefficients.…”

“…1). The relevant molecular organization of the modified surface contains proteins in the bulk and adsorbed in a monolayer, whereas in between them there is a depletion of proteins due to the large repulsions imposed by the grafted polymers (15,17). The free energy is obtained from a molecular approach that we have developed in which the size, shape, conformations, and charge distribution of each molecular species are explicitly accounted for (17,22,23).…”

“…Experimental observations demonstrate that charged proteins may be trapped on poylelectrolyte grafted layers (14). Further, our recent theoretical predictions have shown that model PEG polymer layers can trap proteins adsorbed on hydrophobic surfaces, whenever the film thickness is larger than the protein size (15). Thus, the longer the molecular weight of the polymers forming the layer, at fixed surface coverage, the larger the desorption time.…”

Surface-immobilised antimicrobial peptoids

“…In order to create surfaces with both active antibacterial and passive antifouling properties, we modified surfaces with PMP1-AMP or PMP1-C first and then backfilled with the shorter PMP1 10 . Modifying surfaces with a two-step approach involving grafting of a longer polymer followed by backfilling with a shorter one, has been shown to be an effective strategy for enhancing antifouling performance of polymer brushes (Fang et al, 2005;Satomi et al, 2007;Uchida et al, 2007). In the present case, backfilling with PMP1 10 should facilitate extension of the active AMP moiety away from the surface for interaction with bacteria that encounter the modified surface.…”

Theory of “Selectivity” of label-free nanobiosensors: A geometro-physical perspective

“…The full solution of the two step problem requires three-dimensional simulation of diffusion limited aggregation of finite size particles with excluded volume interactions onto the sensor surface-a computationally challenging problem. 13 A more intuitive and fruitful approach involves modifying the Langmuir model for diffusion limited capture to include the geometry of surface coverage through RSA of the receptor ͑or the target, and parasitic molecules͒, as discussed below. The quality of the approximation can be tested by comparing the theoretical prediction with experimental results.…”