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Hydrophobic interactions drive numerous biological and synthetic processes. The materials used in these processes often possess chemically heterogeneous surfaces that are characterized by diverse chemical groups positioned in close proximity at the nanoscale; examples include functionalized nanomaterials and biomolecules, such as proteins and peptides. Nonadditive contributions to the hydrophobicity of such surfaces depend on the chemical identities and spatial patterns of polar and nonpolar groups in ways that remain poorly understood.