Molecular details of BSA adsorption on a silica surface are revealed by fully atomistic molecular dynamics (MD) simulations (with a 0.5 μs trajectory), supported by dynamic light scattering (DLS), zeta potential, multiparametric surface plasmon resonance (MP-SPR), and contact angle experiments. The experimental and theoretical methods complement one another and lead to a wider understanding of the mechanism of BSA adsorption across a range of pH 3-9. The MD results show how the negatively charged BSA at pH7 adsorbs to the negatively charged silica surface, and reveal a unique orientation with preserved secondary and tertiary structure. The experiments then show that the protein forms complete monolayers at ∼ pH6, just above the protein's isoelectric point (pH5.1). The surface contact angle is maximum when it is completely coated with protein, and the hydrophobicity of the surface is understood in terms of the simulated protein conformation. The adsorption behavior at higher pH > 6 is also consistently interpreted using the MD picture; both the contact angle and the adsorbed protein mass density decrease with increasing pH, in line with the increasing magnitude of negative charge on both the protein and the surface. At lower pH < 5 the protein starts to unfold, and the adsorbed mass dramatically decreases. The comprehensive picture that emerges for the formation of oriented protein films with preserved native conformation will help guide efforts to create functional films for new technologies.

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Polyelectrolytes are abundant in nature and crucial due to their versatility in biological systems. The controlled assembly of polyelectrolytes has potential applications in the formation of nanostructured and microstructured materials of desired structure and functionality. Dendrimers are a special class of polyelectrolytes, which are characterized by their densely branched and well-defined spherical geometry. Amino-terminal dendrimers resemble spheres, whose uniform surface charge densities can be continuously modulated by pH or ionic strength. The present study focuses on the dendrimer monolayer structure on gold surfaces. We used multiparametric surface plasmon resonance (MP-SPR) and a quartz crystal microbalance with dissipation energy monitoring (QCM-D) to investigate the conformational behavior of the sixth generation of PAMAM molecules. Both the kinetics of dendrimer deposition and the maximum surface concentration were determined. The dependence of the maximum coverage on the pH, ionic strength, and the experimental kinetic runs were quantitatively interpreted in terms of the random sequential adsorption (RSA) model using the concept of effective hard particles. It is shown that the MP-SPR measurements can be used to determine the mechanisms of dendrimer adsorption, e.g., the reversibility and orientation of molecules at interfaces. Additionally, this method can be used for a precise determination of dendrimer coverage, hence, its concentration in the bulk solution at levels of 0.05 ppm or less. The extent of hydration of dendrimer films was estimated from the combination of the QCM-D and MP-SPR data, with the assumption that the excess mass measured in QCM-D compared to MP-SPR mass is due to trapped water molecules. The structure of the resulting films is strongly dependent on the deposition conditions.

We study the energy landscape of the negatively charged protein bovine serum albumin adsorbed on a negatively charged silica surface at pH 7. We use fully atomistic molecular dynamics (MD) and steered MD (SMD) to probe the energy of adsorption and the pathway for the surface diffusion of the protein and its associated activation energy. We find an adsorption energy ∼1.2 eV, which implies that adsorption is irreversible even on experimental time scales of hours. In contrast, the activation energy for surface diffusion is ∼0.4 eV so that it is observable on the MD simulation time scale of 100 ns. This analysis paves the way for a more detailed understanding of how a protein layer forms on biomaterial surfaces, even when the protein and surface share the same electrical polarity.