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A classical model in the framework of the INTERFACE force field has been developed for treating the LiCoO$$_2$$ (LCO) (001)/water interface. In comparison to {\em ab initio} molecular dynamics (MD) simulations based on density functional theory, MD simulations using the classical model lead to generally reliable descriptions of interfacial properties, such as the density distribution of water molecules. Water molecules in close contact with the LCO surface form a strongly adsorbed layer, which leads to a free energy barrier for the absorption of polar or charged molecules to the LCO surface. Moreover, due to the strong hydrogen bonding interactions with the LCO surface, the first water layer forms an interface that exhibits hydrophobic characters, leading to favorable adsorption of non-polar molecules to the interface. Therefore, despite its highly polar nature, the LCO (001) surface binds not only polar/charged but also non-polar solutes. As an application, the model is used to analyze the adsorption of reduced nicotinamide adenine dinucleotide (NADH) and its molecular components to the LCO (001) surface in water. The results suggests that recently observed redox activity of NADH at the LCO/water interface was due to the co-operativity between the ribose component, which drives binding to the LCO surface, and the nicotinamide moiety, which undergoes oxidation. 

The molecular features that dictate interactions between functionalized nanoparticles and biomolecules are not well understood. This is in part because for highly charged nanoparticles in solution, establishing a clear connection between the molecular features of surface ligands and common experimental observables such as ζ potential requires going beyond the classical models based on continuum and mean field models. Motivated by these considerations, molecular dynamics simulations are used to probe the electrostatic properties of functionalized gold nanoparticles and their interaction with a charged peptide in salt solutions. Counterions are observed to screen the bare ligand charge to a significant degree even at the moderate salt concentration of 50 mM. As a result, the apparent charge density and ζ potential are largely insensitive to the bare ligand charge densities, which fall in the range of ligand densities typically measured experimentally for gold nanoparticles. While this screening effect was predicted by classical models such as the Manning condensation theory, the magnitudes of the apparent surface charge from microscopic simulations and mean-field models are significantly different. Moreover, our simulations found that the chemical features of the surface ligand ( e.g. , primary vs. quaternary amines, heterogeneous ligand lengths) modulate the interfacial ion and water distributions and therefore the interfacial potential. The importance of interfacial water is further highlighted by the observation that introducing a fraction of hydrophobic ligands enhances the strength of electrostatic binding of the charged peptide. Finally, the simulations highlight that the electric double layer is perturbed upon binding interactions. As a result, it is the bare charge density rather than the apparent charge density or ζ potential that better correlates with binding affinity of the nanoparticle to a charged peptide. Overall, our study highlights the importance of molecular features of the nanoparticle/water interface and underscores a set of design rules for the modulation of electrostatic driven interactions at nano/bio interfaces. 

Quantifying the number of charges on peptides bound to interfaces requires reliable estimates of (i) surface coverage and (ii) surface charge, both of which are notoriously difficult parameters to obtain, especially at solid/water interfaces. Here, we report the thermodynamics and electrostatics governing the interactions of l -lysine and l -arginine octamers (Lys 8 and Arg 8 ) with supported lipid bilayers prepared from a 9 : 1 mixture of 1,2-dimyristoyl- sn-glycero -3-phosphocholine (DMPC) and 1,2-dimyristoyl- sn -glycero-3-phospho-(1′-rac-glycerol) (sodium salt) (DMPG) from second harmonic generation (SHG) spectroscopy, quartz crystal microbalance with dissipation monitoring (QCM-D) and nanoplasmonic sensing (NPS) mass measurements, and atomistic simulations. The combined SHG/QCM-D/NPS approach provides interfacial charge density estimates from mean field theory for the attached peptides that are smaller by a factor of approximately two (0.12 ± 0.03 C m −2 for Lys 8 and 0.10 ± 0.02 C m −2 for Arg 8 ) relative to poly- l -lysine and poly- l -arginine. These results, along with atomistic simulations, indicate that the surface charge density of the supported lipid bilayer is neutralized by the attached cationic peptides. Moreover, the number of charges associated with each attached peptide is commensurate with those found in solution; that is, Lys 8 and Arg 8 are fully ionized when attached to the bilayer. Computer simulations indicate Lys 8 is more likely than Arg 8 to “stand-up” on the surface, interacting with lipid headgroups through one or two sidechains while Arg 8 is more likely to assume a “buried” conformation, interacting with the bilayer through up to six sidechains. Analysis of electrostatic potential and charge distribution from atomistic simulations suggests that the Gouy–Chapman model, which is widely used for mapping surface potential to surface charge, is semi-quantitatively valid; despite considerable orientational preference of interfacial water, the apparent dielectric constant for the interfacial solvent is about 30, due to the thermal fluctuation of the lipid–water interface. 

We describe a strategy of integrating quantum mechanical (QM), hybrid quantum mechanical/molecular mechanical (QM/MM) and MM simulations to analyze the physical properties of a solid/water interface. This protocol involves using a correlated ab initio (CCSD(T)) method to first calibrate Density Functional Theory (DFT) as the QM approach, which is then used in QM/MM simulations to compute relevant free energy quantities at the solid/water interface using a mean-field approximation of Yang et al. that decouples QM and MM thermal fluctuations; gas-phase QM/MM and periodic DFT calculations are used to determine the proper QM size in the QM/MM simulations. Finally, the QM/MM free energy results are compared with those obtained from MM simulations to directly calibrate the force field model for the solid/water interface. This protocol is illustrated by examining the orientations of an alkyl amine ligand at the gold/water interface, since the ligand conformation is expected to impact the chemical properties ( e.g. , charge) of the solid surface. DFT/MM and MM simulations using the INTERFACE force field lead to consistent results, suggesting that the effective gold/ligand interactions can be adequately described by a van der Waals model, while electrostatic and induction effects are largely quenched by solvation. The observed differences among periodic DFT, QM/MM and MM simulations, nevertheless, suggest that explicitly including electronic polarization and potentially charge transfer in the MM model can be important to the quantitative accuracy. The strategy of integrating multiple computational methods to cross-validate each other for complex interfaces is applicable to many problems that involve both inorganic/metallic and organic/biomolecular components, such as functionalized nanoparticles. 

Understanding the mechanisms of nanoparticle interaction with cell membranes is essential for designing materials for applications such as bioimaging and drug delivery, as well as for assessing engineered nanomaterial safety. Much attention has focused on nanoparticles that bind strongly to biological membranes or induce membrane damage, leading to adverse impacts on cells. More subtle effects on membrane function mediated via changes in biophysical properties of the phospholipid bilayer have received little study. Here, we combine electrophysiology measurements, infrared spectroscopy, and molecular dynamics simulations to obtain insight into a mode of nanoparticle-mediated modulation of membrane protein function that was previously only hinted at in prior work. Electrophysiology measurements on gramicidin A (gA) ion channels embedded in planar suspended lipid bilayers demonstrate that anionic gold nanoparticles (AuNPs) reduce channel activity and extend channel lifetimes without disrupting membrane integrity, in a manner consistent with changes in membrane mechanical properties. Vibrational spectroscopy indicates that AuNP interaction with the bilayer does not perturb the conformation of membrane-embedded gA. Molecular dynamics simulations reinforce the experimental findings, showing that anionic AuNPs do not directly interact with embedded gA channels but perturb the local properties of lipid bilayers. Our results are most consistent with a mechanism in which anionic AuNPs disrupt ion channel function in an indirect manner by altering the mechanical properties of the surrounding bilayer. Alteration of membrane mechanical properties represents a potentially important mechanism by which nanoparticles induce biological effects, as the function of many embedded membrane proteins depends on phospholipid bilayer biophysical properties.