Surface-structure-regulated penetration of nanoparticles across a cell membrane

Abstract

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.

Direct Permeation of Nanoparticles across Cell Membrane: A Review

“…The similar free energy change induced by switching from random ligand structure to ordered ligand structure has been also reported by Gkeka et al (2013). Li et al (2012) conducted further analysis for understanding why the NP with striated ligand pattern exhibited the higher permeability. They indicated that the shallow energy minimum of the striated NP is attributed to lower degree of freedom for rotation of the striated NP in the hydrophobic region of the bilayer.…”

“…This issue has been investigated by MD simulation studies. Li et al (2012) investigated the direct permeation of ligand-coated NPs with two different types of ligand structural patterns: striated pattern with orderly arranged hydrophilic and hydrophobic domains ("St" in Fig. 4(a)), and randomly arranged pattern at the same ratio of the hydrophilic and hydrophobic ligands ("Rand" in Fig.…”

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles

“…When the ligands were arranged as stripes, the particles were able to translocate easily across the membrane, while in the random arrangement endocytosis occurred. [147][148][149] Endocytosis serves to absorb molecules from the extracellular space by invagination of the plasma membrane and formation of intracellular vesicles. The first type of endocytosis discovered was clathrin-mediated endocytosis, but in the meantime several additional types of endocytosis have been identified.…”

Advances in The Understanding of Nanomaterial–Biomembrane Interactions and Their Mathematical and Numerical Modeling

“…Studies have found that peptide encapsulated fluorescent silver nanoclusters [49] and polyarginineconjugated iron oxide NMs loaded with siRNA can directly penetrate cell mebranes [55]. Similar to CPPs, several synthetic NMs, such as synthetic amphipathic phospho lipid polymers [56] and nanoparticles (NPs) coated with hydrophilic-hydrophobic striated ligand shell [57,58] can also penetrate the mem brane in a similar manner to the CPPs without disrupting the membrane. Table 1 summarizes the cellular uptake path ways of different NMs.…”