The cell uptake rate of nanoparticles (NPs) coated with mixed hydrophilic/hydrophobic ligands is known to be strongly influenced by the ligand pattern on the nanoparticle surface. To help reveal the physical mechanism behind this intriguing phenomenon, here we perform dissipative particle dynamics simulations to analyze the evolution of free energy as the ligand-coated NPs pierce through a lipid bilayer. Four characteristic ligand patterns are considered: striated NPs with alternating hydrophilic and hydrophobic groups compared to NPs with randomly mixed ligands at the same hydrophilic to hydrophobic ratio, as well as NPs coated with homogeneous hydrophilic or hydrophobic ligands. The free energy analysis indicates that among the four ligand patterns under study, the striated NP encounters the lowest energy barrier during translocation across the membrane. Further analysis reveals that the translocation of the striated NP is facilitated by the constraint of its rotational degree of freedom by the anisotropic ligand pattern, which prevented the free energy of the system from sinking to a deeper valley as the NP passes through the hydrophobic core of the bilayer. Finally, the critical forces required for almost instant penetration of these patterned NPs across the bilayer are calculated and shown to be consistent with the free energy analysis. These findings provide useful guidelines for the molecular design of patterned NPs for controllable cell penetrability.