The hydrophobic effect, and fluctuations: The long and the short of it

The hydrophobic effect, which is used to describe the aversion of oil for water or the affinity of oily objects for one another in water, plays an important role in diverse disciplines (1). For example, by segregating to the oil–water interface, amphiphilic molecules that possess both hydrophobic and hydrophilic groups can mitigate unfavorable oil–water interactions, thereby stabilizing emulsions and facilitating detergency. Because roughly half the amino acids, which form the basic building blocks of proteins, are hydrophobic, the hydrophobic effect also plays a central role in biophysics. Owing to its ubiquity and its multifaceted nature (2, 3), being able to accurately model the hydrophobic effect is both important and challenging. In PNAS, Vaikuntanathan et al. (4) provide important insights into the essential ingredients required in a minimal model of the hydrophobic effect. The hydrophobic effect characteristically manifests itself in very different ways at microscopic and macroscopic length scales (1). Macroscopically, the aversion of oil and water for one another is captured by the large surface tension associated with the oil–water interface. At this scale, the hydrophobic effect drives the minimization of the unfavorable interfacial area (for example, by the coalescence of oil droplets in water). Although the macroscopic hydrophobic effect is governed by the relatively straightforward physics of interfaces, it can nevertheless lead to complex phenomena, such as the nanobubble-mediated long-ranged forces between extended hydrophobic surfaces (5), or the assembly of anisotropic particles at curved interfaces (6). Interestingly, the thermodynamic driving force for such hydrophobic assembly, which is dictated by interfacial tension, decreases with increasing temperature. In contrast, at the molecular scale, the driving force for hydrophobic assembly famously increases with increasing temperature (1). In fact, whenever biomolecular assembly occurs upon increasing temperature, in seeming disregard for entropic considerations, the hydrophobic effect is often the first suspect. A classic …