The cellular membrane functions as a regulating barrier between the intracellular and extracellular regions. For a molecule to reach the interior of the cell from the extracellular fluid, it must diffuse across the membrane, via either active or passive transport. The rigid structure of lipid bilayers, which are a key component of cellular membranes, prohibit simple diffusion of most particles, while vital nutrients are transported to the interior by specific mechanisms, such as ion channels and transport proteins. Although the cellular membrane provides the cell with protection against unwanted toxins that may be in the extracellular medium, some foreign particles can reach the interior of the cell, resulting in irregularities in cellular function. This behavior is particularly noted for permeants with compact molecular structure, suggesting that common nanoscale building blocks, such as fullerenes, may enter into the interior of a cell. To gauge the propensity for such particles to cross the membrane, we have computed the Gibbs free energy of transfer along the axis normal to the bilayer surface for two nanoscale building blocks, C-60 and a hydrogen-terminated polyhedral oligomeric silsequioxane (H-PUSS) monomer, in a hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer using molecular dynamics simulations and potential of mean force calculations. The studies show that C-60 has a substantial energetic preference for the soft polymer region of the lipid bilayer system, below the water/bilayer interface, with a transition energy from bulk water of -19.8 kcal/mol. The transition of C-60 from the bulk water to the center of the bilayer, while also energetically favorable, has to overcome a +5.9 kcal/mol energetic barrier in the hydrophobic lipid tail region. The H-PUSS simulations indicate an energy minimum at the water-bilayer interface, with an energy of -10.9 kcal/mol; however, a local minimum of -2.7 kcal/mol is also observed in the hydrophobic dense aliphatic region. The energy barrier seen in the hydrophobic core region of the C-60 study is likely due to the significant penalty associated with inserting the relatively large particle into such a dense region. In contrast, whereas H-PUSS is found to be subject to an energetic penalty upon insertion into the bilayer, the relatively small size of the H-PUSS solute renders this penalty less significant. The energy barrier seen in the soft polymer region for the H-PUSS monomer is primarily attributed to the lack of favorable solute-bilayer electrostatic interactions, which are present in the interfacial region, and fewer van der Waals interactions in the soft polymer region than the dense aliphatic region. These results indicate that C-60 may partition into the organic phase of the DPPC/water system, given the favorable free energies in the soft polymer and dense aliphatic regions of the bilayer, and H-PUSS is likely to partition near the water-bilayer interface, where the particle has low-energy electrostatic interactions with the polar head groups of the bilayer.