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

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 com...

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Bibliographic Details
Published in:Physical chemistry chemical physics : PCCP 2019, Vol.21 (18), p.9520-9530
Main Authors: Gu, Zonglin, Song, Wei, Liu, Shengtang, Li, Baoyu, Plant, Leigh D, Xuan-Yu, Meng
Format: Article
Language:English
Subjects:
Anions
Biological effects
Computer simulation
Depolarization
Electric potential
Hydrophobicity
Ion channels
Molecular dynamics
Molybdenum disulfide
Nanomaterials
Viability
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Summary: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 (Ψm) 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.
ISSN:1463-9076
1463-9084
DOI:10.1039/c9cp00195f