A Random Sequential Adsorption Model for Protein Adsorption to Surfaces Functionalized with Poly(ethylene oxide (original) (raw)
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Protein Adsorption on Surfaces with Grafted Polymers
Biophysical Journal, 1997
A general theoretical framework for studying the adsorption of protein molecules on surfaces with grafted polymers is presented. The approach is a generalization of the single-chain mean-field theory, in which the grafted polymer-protein-solvent layer is assumed to be inhomogeneous in the direction perpendicular to the grafting surface. The theory enables the calculation of the adsorption isotherms of the protein as a function of the surface coverage of grafted polymers, concentration of protein in bulk, and type of solvent molecules. The potentials of mean force of the protein with the surface are calculated as a function of polymer surface coverage and amount of protein adsorbed. The theory is applied to model lysozyme on surfaces with grafted polyethylene oxide. The protein is modeled as spherical in solution, and it is assumed that the protein-polymer, protein-solvent, and polymer-solvent attractive interactions are all equal. Therefore, the interactions determining the structure of the layer (beyond the bare polymer-surface and protein-surface interactions) are purely repulsive. The bare surface-protein interaction is taken from atomistic calculations by Lee and Park. For surfaces that do not have preferential attractions with the grafted polymer segments, the adsorption isotherms of lysozyme are independent of the polymer length for chains with more than 50 ethylene oxide units. However, the potentials of mean force show strong variations with grafted polymer molecular weight. The competition between different conformations of the adsorbed protein is studied in detail. The adsorption isotherms change qualitatively for surfaces with attractive interactions with ethylene oxide monomers. The protein adsorption is a function of chain length-the longer the polymer the more effective it is in preventing protein adsorption. The structure of the layer and its deformation upon protein adsorption are very important in determining the adsorption isotherms and the potentials of mean force.
Kinetics of Protein Adsorption and Desorption on Surfaces with Grafted Polymers
Biophysical Journal, 2005
The kinetics of protein adsorption are studied using a generalized diffusion approach which shows that the timedetermining 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.
Langmuir, 1998
Prevention of protein adsorption by the surface-grafted poly(ethylene oxide) (PEO) chains has been well-known. We have examined the mechanisms of how the grafted PEO prevents protein adsorption. PEO-poly(propylene oxide)-PEO (PEO-PPO-PEO) triblock copolymers were used to graft PEO to the trichlorovinylsilane (TCVS)-modified glass by γ-irradiation. The surface density of the PEO chains was varied up to 60 pmol/cm 2 and the number of the ethylene oxide (EO) units of the PEO segment was varied from 75 to 128. The adsorption of lysozyme and fibrinogen to the PEO-grafted glass was examined using radiolabeled proteins. The surface protein concentration decreased as the surface density of the grafted PEO increased, but surface protein concentration never reached zero. The experimental data were compared with the predictions by the single-chain mean-field theory. There was very good agreement between the predictions of the theory and the experimental observations. It was found that the mechanism for prevention of protein adsorption by the grafted PEO chains in the hydrophobic surfaces was due to the blocking by the PEO segments of the adsorbing sites of the proteins. The mechanism of the grafted chains to prevent protein adsorption was shown to depend upon the interactions of the surface with the segments of the grafted polymers. Surfaces that did not attract the polymer segments present effective kinetic barriers but were not very good for equilibrium prevention. On the other hand, hydrophobic surfaces, such as the ones used in the experimental work, were very effective for reducing the equilibrium amount of proteins adsorbed. It was found that the most important parameter in preventing protein adsorption by grafted polymers is the surface density of the grafted polymer. The polymer molecular weight, or the chain length, was found to have a weak effect.
Polymer Chain Adsorption on a Solid Surface: Scaling Arguments and Computer Simulations
Springer Series in Surface Sciences, 2010
We examine the phase transition of polymer adsorption as well as the underlying kinetics of polymer binding from dilute solutions on a structureless solid surface. The emphasis is put on the properties of regular multiblock copolymers, characterized by block size M and total length N as well as on random copolymers with quenched composition p of sticky and neutral segments. The macromolecules are modeled as coarse-grained bead-spring chains subject to a short-ranged surface adhesive potential. Phase diagrams, showing the variation of the critical threshold for single chain adsorption in terms of M and p are derived from scaling considerations in agreement with results from computer experiment.
Title : Understanding Protein Adsorption Phenomena at Solid Surfaces
2011
Protein adsorption at solid surfaces plays a key role in many natural processes and has therefore promoted a widespread interest in many research areas. Despite considerable progress in this field there are still widely differing and even contradictive opinions on how to explain the frequently observed phenomena such as structural rearrangements, cooperative adsorption, overshooting adsorption kinetics, or protein aggregation. In this review recent achievements and new perspectives on protein adsorption processes are comprehensively discussed. The main focus is put on commonly postulated mechanistic aspects and their translation into mathematical concepts and model descriptions. Relevant experimental and computational strategies to practically approach the field of protein adsorption mechanisms and their impact on current successes are outlined.
Quantifying and understanding protein adsorption to non-fouling surfaces
2010
Surfaces grafted with poly(ethylene oxide) (PEO) are known to resist protein adsorption. Research efforts in this field have focused on both developing surfaces with better resistance to protein adsorption and understanding the origin of resistance of PEO grafted surfaces to protein adsorption. In the first part of this contribution, we describe a novel quantification technique for extremely low protein coverage on surfaces. This technique utilizes measurement of the landing rate of microtubule filaments on kinesin proteins adsorbed on a surface to determine the kinesin density. The detection limit of our technique is 100 times lower than that of standard characterization methods and is employed to test the performance of novel and established coatings with outstanding resistance to protein adsorption. In the second part, a random sequential adsorption (RSA) model is presented for protein adsorption to PEO coated surfaces. The model suggests that PEO chains act as almost perfect steric barriers to protein adsorption. Furthermore, it can be used to predict the performance of a variety of systems towards resisting protein adsorption and can help in the design of better nonfouling surface coatings. replacement therapies Abstract-PLGA (poly-lactic-co-glycolic acid) has been widely used as a biomaterial in regenerative medicine due to its biocompatibility and biodegradability. The purpose of the present in vitro research was to prepare PLGA films with various nanometer surface features and determine whether lung cancer epithelial cells respond differently to such topographies. Different size polystyrene beads were used to cast poly(dimethylsiloxane) (PDMS) molds which were used as templates to create nano-featured PLGA films. Atomic force microscopy (AFM) images and root mean square (RMS) roughness values indicated that the intended spherical surface nano-topographies on PLGA were formed. A solution evaporation method was also utilized to modify PLGA surface features by using 8 wt % and 4 % chloroform solutions. Most importantly, lung cancer epithelial cells adhered less on the PLGA surfaces with RMS values of 0.62, 2.23 and 5.42 nm after 4 hours of culture compared to any other PLGA surface created here. After 3 days, PLGA surfaces with an RMS value of 0.62 nm had much lower cell density than any other sample. In this manner, PLGA with specific nanometer surface features may inhibit lung cancer cell density, providing an important biomaterial for the treatment of lung cancer with wide range of applications.
Kinetic and thermodynamic control of protein adsorption
Proceedings of the National Academy of Sciences, 2000
Control of nonspecific protein adsorption is very important for the design of biocompatible and biomimetic materials as well as drug carriers. Grafted polymer layers can be used to prevent protein adsorption. We have studied the molecular factors that determine the equilibrium and kinetic control of protein adsorption by grafted polymer layers. We find that polymers that are not attracted to the surface are very effective for kinetic control but not very good for equilibrium reduction of protein adsorption. Polymers with attractions to the surface show exactly the opposite behavior. The implications for molecular design of biocompatible materials also are discussed in this paper.
Langmuir, 2011
A combined experimental and theoretical approach establishes the long-lived nature of protein adsorption on surfaces coated with chemically-grafted macromolecules. Specifically, we monitor the time dependence of adsorption of lysozyme on surfaces comprising polymer assemblies made of poly(2-hydroxyethyl methacrylate) brushes grafted onto flat silica surfaces such that they produce patterns featuring orthogonal and gradual variation of the chain length (N) and grafting density (σ). We show that in the kinetically-controlled regime the amount of adsorbed protein scales universally with the product σN while at equilibrium the amount of adsorbed protein is governed solely by σ. Surprisingly, for moderate concentrations of protein in solution, adsorption takes more than 72 hours to reach an equilibrium, or steady state. Our experimental findings are corroborated with predictions using molecular theory that provides further insight into the protein adsorption phenomenon. The theory predicts that the experimentally universal observed behavior should be applicable to polymers in poor and theta solvents and to a limited extent also to good solvents. Our combined experimental and theoretical findings reveal that protein adsorption is a long-lived phenomenon, much longer than generally assumed. Our studies confirm the previously predicted important differences in behavior for the kinetic versus thermodynamic control of protein adsorption.
Understanding protein adsorption phenomena at solid surfaces
Advances in Colloid and Interface Science, 2011
Protein adsorption at solid surfaces plays a key role in many natural processes and has therefore promoted a widespread interest in many research areas. Despite considerable progress in this field there are still widely differing and even contradictive opinions on how to explain the frequently observed phenomena such as structural rearrangements, cooperative adsorption, overshooting adsorption kinetics, or protein aggregation. In this review recent achievements and new perspectives on protein adsorption processes are comprehensively discussed. The main focus is put on commonly postulated mechanistic aspects and their translation into mathematical concepts and model descriptions. Relevant experimental and computational strategies to practically approach the field of protein adsorption mechanisms and their impact on current successes are outlined.
Sticking coefficients of adsorbing proteins
Biomaterials, 1992
The protein sticking coefficient, 4, the fraction of collisions that result in adsorption, is a function of the molecular interactions between the protein and the surface. A random walk and diffusionto-capture model was used to describe the kinetics of protein adsorption. The assumption of a constant sticking coefficient leads to a first-order model of the kinetics. A solution of the problem of adsorption from a semi-infinite medium with first-order kinetics at the boundary was obtained by numerical simulation on the computer. The results of the computer simulations match the time dependence observed experimentally. A correlation was developed to estimate C#J from experimental data. I#J has been found to be in the range 10-5-10-* for several protein adsorption kinetic studies reported in the literature.