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Title: Graphene-extracted membrane lipids facilitate the activation of integrin αvβ8

Abstract

Despite the remarkable electrochemical properties of graphene, strong van der Waals attraction between graphene and biomolecules often causes cytotoxicity, which hinders its applications in the biomedical field. Unfortunately, surface passivation of graphene might stimulate undesired immune response as the nanomaterial triggers cytokine production through membrane receptor activation. In this work, we use all-atom Molecular Dynamics (MD) simulations to unravel the underlying mechanism of graphene-induced inside-out activation of integrin αvβ8, a prominent membrane receptor expressed in immune cells. We model the transmembrane (TM) domains of integrin αvβ8 in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer and observe the structural changes in the integrin–membrane complex when interacting with a graphene nanosheet across the membrane. We find that the β8 TM domain interacts with the graphene nanosheet directly or indirectly through extracted lipids, facilitating the pulling of a β8 subunit away from an αv subunit and thus leading to the disruption of the TM domain association by breaking the hydrophobic cluster in the cytoplasmic domains of the αv and β8 subunits. Alanine substitution of two conserved phenylalanine residues on the αv subunit at this hydrophobic cluster further reveals the importance of a stable T-shaped structure in retaining integrin in its inactive state. Our results agreemore » with previous studies on the interactions between other integrin subtypes and their endogenous activators, suggesting an intriguing role that the graphene nanosheet may play in the integrin-related signal transduction during its interaction with the membrane.« less

Authors:
ORCiD logo [1];  [2];  [3]
  1. IBM Thomas J. Watson Research Center, Yorktown Heights, NY (United States)
  2. Meritorious Autonomous Univ. of Puebla (BUAP), University City, Puebla (Mexico)
  3. IBM Thomas J. Watson Research Center, Yorktown Heights, NY (United States); Zhejiang Univ., Hangzhou (China)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE; W. M. Keck Foundation; IBM Blue Gene Science Program
OSTI Identifier:
1615781
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Nanoscale
Additional Journal Information:
Journal Volume: 12; Journal Issue: 14; Journal ID: ISSN 2040-3364
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Chen, Serena, Perez-Aguilar, Jose Manuel, and Zhou, Ruhong. Graphene-extracted membrane lipids facilitate the activation of integrin αvβ8. United States: N. p., 2020. Web. doi:10.1039/C9NR10469K.
Chen, Serena, Perez-Aguilar, Jose Manuel, & Zhou, Ruhong. Graphene-extracted membrane lipids facilitate the activation of integrin αvβ8. United States. doi:https://doi.org/10.1039/C9NR10469K
Chen, Serena, Perez-Aguilar, Jose Manuel, and Zhou, Ruhong. Sun . "Graphene-extracted membrane lipids facilitate the activation of integrin αvβ8". United States. doi:https://doi.org/10.1039/C9NR10469K. https://www.osti.gov/servlets/purl/1615781.
@article{osti_1615781,
title = {Graphene-extracted membrane lipids facilitate the activation of integrin αvβ8},
author = {Chen, Serena and Perez-Aguilar, Jose Manuel and Zhou, Ruhong},
abstractNote = {Despite the remarkable electrochemical properties of graphene, strong van der Waals attraction between graphene and biomolecules often causes cytotoxicity, which hinders its applications in the biomedical field. Unfortunately, surface passivation of graphene might stimulate undesired immune response as the nanomaterial triggers cytokine production through membrane receptor activation. In this work, we use all-atom Molecular Dynamics (MD) simulations to unravel the underlying mechanism of graphene-induced inside-out activation of integrin αvβ8, a prominent membrane receptor expressed in immune cells. We model the transmembrane (TM) domains of integrin αvβ8 in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer and observe the structural changes in the integrin–membrane complex when interacting with a graphene nanosheet across the membrane. We find that the β8 TM domain interacts with the graphene nanosheet directly or indirectly through extracted lipids, facilitating the pulling of a β8 subunit away from an αv subunit and thus leading to the disruption of the TM domain association by breaking the hydrophobic cluster in the cytoplasmic domains of the αv and β8 subunits. Alanine substitution of two conserved phenylalanine residues on the αv subunit at this hydrophobic cluster further reveals the importance of a stable T-shaped structure in retaining integrin in its inactive state. Our results agree with previous studies on the interactions between other integrin subtypes and their endogenous activators, suggesting an intriguing role that the graphene nanosheet may play in the integrin-related signal transduction during its interaction with the membrane.},
doi = {10.1039/C9NR10469K},
journal = {Nanoscale},
number = 14,
volume = 12,
place = {United States},
year = {2020},
month = {3}
}

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