Final answer:
The hydrophilic nature of ligands of cell-surface receptors prevents them from penetrating the hydrophobic cell membrane.
Step-by-step explanation:
The property that prevents the ligands of cell-surface receptors from entering the cell is their hydrophilic nature. This property makes it difficult for these molecules to penetrate the hydrophobic interior of the cell membrane. In contrast, small hydrophobic ligands, which are generally lipid-soluble, can readily diffuse through the plasma membrane and interact with internal receptors. Examples of such hydrophobic ligands include steroid hormones like estrogen and testosterone.