Understanding Hydrophobic Effects: Insights from Water Density Fluctuations

TL;DR

This paper reviews how water density fluctuations inform our understanding of hydrophobic effects, impacting molecular interactions, surface properties, and protein behavior across scientific disciplines.

Contribution

It synthesizes theoretical, computational, and experimental insights into hydrophobic effects, emphasizing the role of water density fluctuations in diverse contexts.

Findings

Density fluctuations explain differences in hydration of molecular vs. macroscopic solutes.

Hydrophobic interactions strengthen with increasing temperature.

Surface heterogeneity influences hydrophobicity and interaction dynamics.

Abstract

The aversion of hydrophobic solutes for water drives diverse interactions and assemblies across materials science, biology and beyond. % Here, we review the theoretical, computational and experimental developments which underpin a contemporary understanding of hydrophobic effects. % We discuss how an understanding of density fluctuations in bulk water can shed light on the fundamental differences in the hydration of molecular and macroscopic solutes; these differences, in turn, explain why hydrophobic interactions become stronger upon increasing temperature. We also illustrate the sensitive dependence of surface hydrophobicity on the chemical and topographical patterns the surface displays, which makes the use approximate approaches for estimating hydrophobicity particularly challenging. Importantly, the hydrophobicity of complex surfaces, such as those of proteins, which display nanoscale heterogeneity, can nevertheless be characterized using interfacial water density fluctuations; such a characterization also informs protein regions that mediate their interactions. Finally, we build upon an understanding of hydrophobic hydration and the ability to characterize hydrophobicity to inform the context-dependent thermodynamic forces that drive hydrophobic interactions and the desolvation barriers that impede them.