Potential blockade of the human voltage-dependent anion channel by MoS2 nanoflakes

Abstract

Despite significant interest in molybdenum disulfide (MoS₂) nanomaterials, particularly in biomedicine, their biological effects have been understudied. Here, we explored the effect of MoS₂ nanoflakes on the ubiquitous mitochondrial porin voltage-dependent anion channel (VDAC1), using a combined computational and functional approach. All-atomic molecular dynamics simulations suggest that MoS₂ nanoflakes make specific contact interactions with human VDAC1. We show that the initial contacts between hVDAC1 and the nanoflake are hydrophobic but are subsequently enhanced by a complex interplay of van der Waals (vdW), hydrophobic and electrostatic interactions in the equilibrium state. Moreover, the MoS₂ nanoflake can insert into the lumen of the hVDAC1 pore. Free-energy calculations computed by the potential of mean force (PMF) verify that the blocked configuration of the MoS₂–hVDAC1 complex is more energetically favorable than the non-blocked binding mode. Consistent with these predictions, we showed that MoS₂ depolarizes the mitochondrial membrane potential (Ψ_m) and causes a decrease in the viability of mammalian tissue culture cells. These findings might shed new light on the potential biological effect of MoS₂ nanomaterials.