J. Phys. Chem. Lett., 8, 4069–4076 (2017).
Chan-Fei Su, Holger Merlitz, Hauke Rabbel, and Jens-Uwe Sommer
Using coarse-grained molecular dynamics simulations, we study the passive translocation of nanoparticles with a size of about 1 nm and with tunable degrees of hydrophobicity through lipid bilayer membranes. We observe a window of translocation with a sharp maximum for nanoparticles having a hydrophobicity in between hydrophilic and hydrophobic. Passive translocation can be identified as diffusive motion of individual particles in a free energy landscape. By combining direct sampling with umbrella-sampling techniques we calculate the free energy landscape for nanoparticles covering a wide range of hydrophobicities. We show that the directly observed translocation rate of the nanoparticles can be mapped to the mean-escape-rate through the calculated free energy landscape, and the maximum of translocation can be related with the maximally flat free energy landscape. The limiting factor for the translocation rate of nanoparticles having an optimal hydrophobicity can be related with a trapping of the particles in the surface region of the membrane. Here, hydrophobic contacts can be formed but the free energy effort of insertion into the brush-like tail regions can still be avoided. The latter forms a remaining barrier of a few kBT and can be spontaneously surmounted. We further investigate cooperative effects of a larger number of nanoparticles and their impact on the membrane properties such as solvent permeability, area per lipid, and the orientation order of the tails. By calculating the partition of nanoparticles at the phase boundary between water and oil, we map the microscopic parameter of nanoparticle hydrophobicity to an experimentally accessibly partition coefficient. Our studies reveal a generic mechanism for spherical nanoparticles to overcome biological membrane-barriers without the need of biologically activated processes.