Kinetics of protein adsorption and desorption on surfaces with grafted polymers
Kinetics of protein adsorption and desorption on surfaces with grafted polymers
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DOI：
10.1529/biophysj.104.055079
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发表时间：
2005-09-01
影响因子：
3.4
通讯作者：
Szleifer, I
中科院分区：
文献类型：
--
作者：
Fang, F;Satulovsky, J;Szleifer, I
蛋白质吸附的动力学研究使用广义扩散的方法，这表明，在吸附的时间决定步骤是由聚合物和已经吸附的蛋白质所提出的动力学障碍的交叉。由于蛋白质吸附时聚合物层的变形，吸附蛋白质和聚合物-蛋白质表面之间的平均力的电势作为时间的函数而变化。此外，接近蛋白质的排斥相互作用的范围和强度随着接枝聚合物分子量和表面覆盖度的增加而增加。分子量对动力学的影响是非常复杂的，不同于它对平衡吸附等温线的作用。动力学势垒很大，吸附过程的时间尺度很长，计算工作量随时间增加，因此，一个近似的动力学方法。动力学理论是基于这样的知识，即决定时间的步骤是跨越平均力势的障碍。两种状态（吸附和散装）的动力学方程被写入的动力学系数的产品的玻尔兹曼因子的吸附（解吸）的自由能乘以一个前指数因子从Kramers-样的理论。从动力学方法的预测是在良好的定量协议与全扩散方程的解决方案，证明了两个最重要的物理过程是跨越的障碍和障碍随时间的变化，由于变形的聚合物层的蛋白质吸附/解吸。动力学系数可以事先计算，从而允许在非常长的时间尺度上进行系统计算。结果表明，在许多情况下，平衡吸附表现出一个有限的值，该过程的动力学是如此之慢，实验系统将显示没有吸附。这种效应在高接枝聚合物表面覆盖率下特别重要。示出了在所需的时间尺度内动态防止蛋白质吸附所需的分子量/表面覆盖率的准则的构建。还通过模拟吸附的蛋白质与纯水溶液接触时如何离开表面来研究与时间相关的脱附。结果发现，脱附动力学是非常缓慢的，并依赖于在一个非单调的方式在聚合物链的长度。当聚合物层厚度小于蛋白质的尺寸时，在固定的表面覆盖率下，增加聚合物链长度使解吸过程更快。对于厚度大于蛋白质尺寸的聚合物层，分子量的增加导致更长的解吸时间。这是由于接枝聚合物捕获吸附的蛋白质并减缓解吸过程。这些结果为某些吸附实验数据提供了可能的解释。限制和扩展的实际应用中开发的方法进行了讨论。
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.