(253bn) Multiscale Simulations of Protein Adsorption on Self-Assembled Monolayers

Protein adsorption plays an important role not only in a wide range of basic biological processes but also in many applications such as protein chromatography, drug delivery on solid substrates, biosensors, biofuel cells and biomaterials. The ability to tailor both head and tail groups of self-assembled monolayers (SAMs) makes them excellent systems for the fundamental understanding of protein adsorption. We investigated the adsorption behavior of various proteins (such as neuromedin-B, prototypical and mutated protein G B1, lysozyme, ribonuclease A, lipase, hydrophobin, cytochrome c, laccase, feruloyl esterase, and fibrinogen) on the SAMs terminated with different functional groups (such as methyl, hydroxyl, carboxyl, amino, sulfonate, sulfobetaine, phosphorylcholine, and mixed carboxyl/trimethylamino) under different conditions (such as pH, ionic strength (IS), ionic type, surface charge density (SCD), and external electric fields (EFs)) at the microscopic and mesoscopic scales using a combined parallel tempering Monte Carlo (PTMC) algorithm, coarse-grained molecular dynamics (CGMD), and all-atom molecular dynamics (AAMD) simulations. The results indicate that: (i) the conformation change of a protein on the hydrophobic surface is relatively bigger; (ii) the nonspecific protein adsorption can be resisted by the zwitterionic surface due to the tightly bounded water molecules; (iii) the electrostatic interactions between a protein and a charged surface are weakened when the ionic strength increases; (iv) a counterion layer will be formed near the surface when the SCD and IS are high, which can mediate the adsorption of a protein with the same sign of net charge; (v) the orientation of a protein adsorbed on a charged/neutral surface is dominated by its electric/hydrophobic dipole; (vi) the external electric fields can modulate protein adsorption behaviors on the charged surfaces. Our work might provide some guidance for the design of novel ligands for protein purification, design of medical materials with better biocompatibility, improving the efficiency and activity of the immobilized enzymes, the design of biosensors with better responsiveness, and design of antifouling materials with stronger ability in resisting protein adsorption.