Elucidating collective translocation of nanoparticles across the skin lipid matrix: a molecular dynamics study

The top layer of skin, the stratum corneum, provides a formidable barrier to the skin. Nanoparticles are utilized and further explored for personal and health care applications related to the skin. In the past few years, several researchers have studied the translocation and permeation of nanoparticles of various shapes, sizes, and surface chemistry through cell membranes. Most of these studies focused on a single nanoparticle and a simple bilayer system, whereas skin has a highly complex lipid membrane architecture. Moreover, it is highly unlikely that a nanoparticle formulation applied on the skin will not have multiple nanoparticle-nanoparticle and skin-nanoparticle interactions. In this study, we have utilized coarse-grained MARTINI molecular dynamics simulations to assess the interactions of two types (bare and dodecane-thiol coated) of nanoparticles with two models (single bilayer and double bilayer) of skin lipid membranes. The nanoparticles were found to be partitioned from the water layer to the lipid membrane as an individual entity as well as in the cluster form. It was discovered that each nanoparticle reached the interior of both single bilayer and double bilayer membranes irrespective of the nanoparticle type and concentration, though coated particles were observed to efficiently traverse across the bilayer when compared with bare particles. The coated nanoparticles also created a single large cluster inside the membrane, whereas the bare nanoparticles were found in small clusters. Both the nanoparticles exhibited preferential interactions with cholesterol molecules present in the lipid membrane as compared to other lipid components of the membrane. We have also observed that the single membrane model exhibited unrealistic instability at moderate to higher concentrations of nanoparticles, and hence for translocation study, a minimum double bilayer model should be employed.