Sitting at the edge: How biomolecules use hydrophobicity to tune their interactions and function

Water near hydrophobic surfaces is like that at a liquid-vapor interface, where fluctuations in water density are substantially enhanced compared to that in bulk water. Here we use molecular simulations with specialized sampling techniques to show that water density fluctuations are similarly enhanced, even near hydrophobic surfaces of complex biomolecules, situating them at the edge of a dewetting transition. Consequently, water near these surfaces is sensitive to subtle changes in surface conformation, topology, and chemistry, any of which can tip the balance towards or away from the wet state, and thus significantly alter biomolecular interactions and function. Our work also resolves the long-standing puzzle of why some biological surfaces dewet and other seemingly similar surfaces do not.Comment: 12 pages, 4 figure

A Molecular Thermodynamic Model of Coacervation in Solutions of Polycations and Oppositely Charged Micelles

To guide the rational design of personal care formulations, we formulate a molecular thermodynamic model that predicts coacervation from cationic polymers and mixed micelles containing neutral and anionic surfactants and added salt. These coacervates, which form as a result of dilution of conditioning shampoos during use, deposit conditioning agents and other actives to the scalp or skin and also provide lubrication benefits. Our model accounts for mixing entropy, hydrophobic interactions of polycation with water, free energies of bindings of oppositely charged groups to micelles and polycations, and electrostatic interactions that capture connectivity of charged groups on the polycation chain and the micelle. The model outputs are the compositions of surfactants, polycation, salt, and water in the coacervate and in its coexisting dilute phase, along with the binding fractions and coacervate volume fraction. We study the effects of overall composition (of surfactant, polycation, and added salt), charge fractions on micelles and polycations, and binding free energies on the phase diagram of coacervates. Then, we perform coacervation experiments for three systems: sodium dodecyl sulfate (SDS)–JR30M, sodium methyl cocoyl taurate (Taurate)–JR30M, and sodium lauryl alaninate (Alaninate)–JR30M, where JR30M is a cationic derivative of hydroxyethylcellulose (cat-HEC), and rationalize their coacervation data using our model. For comparison with experiment, we also develop a parametrization scheme to obtain the requisite binding energies and Flory–Huggins χ parameter. We find that our model predictions agree reasonably well with the experimental data, and that the sulfate-free surfactants of Taurate and Alaninate display much larger 2-phase regions compared to SDS with JR30M

Sitting at the Edge: How Biomolecules use Hydrophobicity to Tune Their Interactions and Function

Water near extended hydrophobic surfaces is like that at a liquid–vapor interface, where fluctuations in water density are substantially enhanced compared to those in bulk water. Here we use molecular simulations with specialized sampling techniques to show that water density fluctuations are similarly enhanced, even near hydrophobic surfaces of complex biomolecules, situating them at the edge of a dewetting transition. Consequently, water near these surfaces is sensitive to subtle changes in surface conformation, topology, and chemistry, any of which can tip the balance toward or away from the wet state and thus significantly alter biomolecular interactions and function. Our work also resolves the long-standing puzzle of why some biological surfaces dewet and other seemingly similar surfaces do not

Probing Additive Loading in the Lamellar Phase of a Nonionic Surfactant: Gibbs Ensemble Monte Carlo Simulations Using the SDK Force Field

Understanding solute uptake into soft microstructured materials, such as bilayers and worm-like and spherical micelles, is of interest in the pharmaceutical, agricultural, and personal care industries. To obtain molecular-level insight on the effects of solutes loading into a lamellar phase, we utilize the Shinoda–Devane–Klein (SDK) coarse-grained force field in conjunction with configurational-bias Monte Carlo simulations in the osmotic Gibbs ensemble. The lamellar phase is comprised of a bilayer formed by triethylene glycol mono-<i>n</i>-decyl ether (C10E3) surfactants surrounded by water with a 50:50 surfactant/water weight ratio. We study both the unary adsorption isotherm and the effects on bilayer structure and stability caused by <i>n</i>-nonane, 1-hexanol, and ethyl butyrate at several different reduced reservoir pressures. The nonpolar <i>n</i>-nonane molecules load near the center of the bilayer. In contrast, the polar 1-hexanol and ethyl butyrate molecules both load with their polar bead close to the surfactant head groups. Near the center of the bilayer, none of the solute molecules exhibits a significant orientational preference. Solute molecules adsorbed near the polar groups of the surfactant chains show a preference for orientations perpendicular to the interface, and this alignment with the long axis of the surfactant molecules is most pronounced for 1-hexanol. Loading of <i>n</i>-nonane leads to an increase of the bilayer thickness, but does not affect the surface area per surfactant. Loading of polar additives leads to both lateral and transverse swelling. The reduced Henry’s law constants of adsorption (expressed as a molar ratio of additive to surfactant per reduced pressure) are 0.23, 1.4, and 14 for <i>n</i>-nonane, 1-hexanol, and ethyl butyrate, respectively, and it appears that the SDK force field significantly overestimates the ethyl butyrate–surfactant interactions