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 »
- Authors:
-
[1];
- IBM Thomas J. Watson Research Center, Yorktown Heights, NY (United States)
- Meritorious Autonomous Univ. of Puebla (BUAP), University City, Puebla (Mexico)
- 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. 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. 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 = {Sun Mar 01 00:00:00 EST 2020},
month = {Sun Mar 01 00:00:00 EST 2020}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 11 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Structural Basis of Integrin Activation by Talin
journal, January 2007
- Wegener, Kate L.; Partridge, Anthony W.; Han, Jaewon
- Cell, Vol. 128, Issue 1
Bilayer Thickness and Membrane Protein Function: An Energetic Perspective
journal, June 2007
- Andersen, Olaf S.; Koeppe, Roger E.
- Annual Review of Biophysics and Biomolecular Structure, Vol. 36, Issue 1
Understanding biophysicochemical interactions at the nano–bio interface
journal, June 2009
- Nel, Andre E.; Mädler, Lutz; Velegol, Darrell
- Nature Materials, Vol. 8, Issue 7
Breaking the Integrin Hinge: A DEFINED STRUCTURAL CONSTRAINT REGULATES INTEGRIN SIGNALING
journal, March 1996
- Hughes, Paul E.; Diaz-Gonzalez, Federico; Leong, Lilley
- Journal of Biological Chemistry, Vol. 271, Issue 12
How lipids affect the activities of integral membrane proteins
journal, November 2004
- Lee, Anthony G.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1666, Issue 1-2
Scalable molecular dynamics with NAMD
journal, January 2005
- Phillips, James C.; Braun, Rosemary; Wang, Wei
- Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
Nanoparticle-mediated cellular response is size-dependent
journal, March 2008
- Jiang, Wen; Kim, Betty Y. S.; Rutka, James T.
- Nature Nanotechnology, Vol. 3, Issue 3
Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets
journal, July 2013
- Tu, Yusong; Lv, Min; Xiu, Peng
- Nature Nanotechnology, Vol. 8, Issue 8
Synthesis of graphene
journal, February 2016
- Bhuyan, Md. Sajibul Alam; Uddin, Md. Nizam; Islam, Md. Maksudul
- International Nano Letters, Vol. 6, Issue 2
Comprehensive analysis of sequences of a protein switch: Analysis of Sequences of a Protein Switch
journal, July 2015
- Chen, Szu-Hua; Meller, Jaroslaw; Elber, Ron
- Protein Science, Vol. 25, Issue 1
PEGylated graphene oxide elicits strong immunological responses despite surface passivation
journal, February 2017
- Luo, Nana; Weber, Jeffrey K.; Wang, Shuang
- Nature Communications, Vol. 8, Issue 1
Integrins in immunity
journal, December 2008
- Evans, R.; Patzak, I.; Svensson, L.
- Journal of Cell Science, Vol. 122, Issue 2
Phospholipid Membrane Fluidity Alters Ligand Binding Activity of a G Protein-Coupled Receptor by Shifting the Conformational Equilibrium
journal, December 2018
- Yoshida, Kouhei; Nagatoishi, Satoru; Kuroda, Daisuke
- Biochemistry, Vol. 58, Issue 6
Computational close up on protein-protein interactions: how to unravel the invisible using molecular dynamics simulations?: Computational close up on protein-protein interactions
journal, July 2015
- Rakers, Christin; Bermudez, Marcel; Keller, Bettina G.
- Wiley Interdisciplinary Reviews: Computational Molecular Science, Vol. 5, Issue 5
The final steps of integrin activation: the end game
journal, April 2010
- Shattil, Sanford J.; Kim, Chungho; Ginsberg, Mark H.
- Nature Reviews Molecular Cell Biology, Vol. 11, Issue 4
Comparison of simple potential functions for simulating liquid water
journal, July 1983
- Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
- The Journal of Chemical Physics, Vol. 79, Issue 2
A Specific Interface between Integrin Transmembrane Helices and Affinity for Ligand
journal, June 2004
- Luo, Bing-Hao; Springer, Timothy A.; Takagi, Junichi
- PLoS Biology, Vol. 2, Issue 6
Integrin activation by talin, kindlin and mechanical forces
journal, January 2019
- Sun, Zhiqi; Costell, Mercedes; Fässler, Reinhard
- Nature Cell Biology, Vol. 21, Issue 1
Surface Polyethylene Glycol Conformation Influences the Protein Corona of Polyethylene Glycol-Modified Single-Walled Carbon Nanotubes: Potential Implications on Biological Performance
journal, February 2013
- Sacchetti, Cristiano; Motamedchaboki, Khatereh; Magrini, Andrea
- ACS Nano, Vol. 7, Issue 3
Biomolecular Modeling: Goals, Problems, Perspectives
journal, June 2006
- van Gunsteren, Wilfred F.; Bakowies, Dirk; Baron, Riccardo
- Angewandte Chemie International Edition, Vol. 45, Issue 25
Nonequilibrium Equality for Free Energy Differences
journal, April 1997
- Jarzynski, C.
- Physical Review Letters, Vol. 78, Issue 14
Hydrogen Bond Networks in Graphene Oxide Composite Paper: Structure and Mechanical Properties
journal, March 2010
- Medhekar, Nikhil V.; Ramasubramaniam, Ashwin; Ruoff, Rodney S.
- ACS Nano, Vol. 4, Issue 4
The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation
journal, October 1999
- Calderwood, David A.; Zent, Roy; Grant, Richard
- Journal of Biological Chemistry, Vol. 274, Issue 40
Lipid fluidity and membrane protein dynamics
journal, November 1987
- Lenaz, Giorgio
- Bioscience Reports, Vol. 7, Issue 11
OPM database and PPM web server: resources for positioning of proteins in membranes
journal, September 2011
- Lomize, Mikhail A.; Pogozheva, Irina D.; Joo, Hyeon
- Nucleic Acids Research, Vol. 40, Issue D1
The structure of the integrin αIIbβ3 transmembrane complex explains integrin transmembrane signalling
journal, March 2009
- Lau, Tong-Lay; Kim, Chungho; Ginsberg, Mark H.
- The EMBO Journal, Vol. 28, Issue 9
Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins
journal, September 2003
- Kim, M.
- Science, Vol. 301, Issue 5640
Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types
journal, June 2010
- Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo
- The Journal of Physical Chemistry B, Vol. 114, Issue 23
Biomolecular Simulation: A Computational Microscope for Molecular Biology
journal, June 2012
- Dror, Ron O.; Dirks, Robert M.; Grossman, J. P.
- Annual Review of Biophysics, Vol. 41, Issue 1
A Structural Mechanism of Integrin αIIbβ3 “Inside-Out” Activation as Regulated by Its Cytoplasmic Face
journal, September 2002
- Vinogradova, Olga; Velyvis, Algirdas; Velyviene, Asta
- Cell, Vol. 110, Issue 5
Empirical force fields for biological macromolecules: Overview and issues
journal, January 2004
- Mackerell, Alexander D.
- Journal of Computational Chemistry, Vol. 25, Issue 13
Structure of Graphite Oxide Revisited ‖
journal, June 1998
- Lerf, Anton; He, Heyong; Forster, Michael
- The Journal of Physical Chemistry B, Vol. 102, Issue 23
Revisiting Hydrophobic Mismatch with Free Energy Simulation Studies of Transmembrane Helix Tilt and Rotation
journal, July 2010
- Kim, Taehoon; Im, Wonpil
- Biophysical Journal, Vol. 99, Issue 1
Multiscale simulations suggest a mechanism for integrin inside-out activation
journal, July 2011
- Kalli, A. C.; Campbell, I. D.; Sansom, M. S. P.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 29
Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading
journal, June 2019
- Kalappurakkal, Joseph Mathew; Anilkumar, Anupama Ambika; Patra, Chandrima
- Cell, Vol. 177, Issue 7
Charging nanoparticles: increased binding of Gd@C 82 (OH) 22 derivatives to human MMP-9
journal, January 2018
- Chen, Serena H.; Kang, Seung-gu; Luo, Judong
- Nanoscale, Vol. 10, Issue 12
Interfacing proteins with graphitic nanomaterials: from spontaneous attraction to tailored assemblies
journal, January 2015
- De Leo, Federica; Magistrato, Alessandra; Bonifazi, Davide
- Chemical Society Reviews, Vol. 44, Issue 19
Atomic Structure of Reduced Graphene Oxide
journal, April 2010
- Gómez-Navarro, Cristina; Meyer, Jannik C.; Sundaram, Ravi S.
- Nano Letters, Vol. 10, Issue 4
Biopharmaceutics and Therapeutic Potential of Engineered Nanomaterials
journal, October 2008
- Liang, Xing-Jie; Chen, Chunying; Zhao, Yuliang
- Current Drug Metabolism, Vol. 9, Issue 8
The energy landscape of a protein switch
journal, January 2014
- Chen, Szu-Hua; Elber, Ron
- Physical Chemistry Chemical Physics, Vol. 16, Issue 14
Probing the Thermal Deoxygenation of Graphene Oxide Using High-Resolution In Situ X-ray-Based Spectroscopies
journal, August 2011
- Ganguly, Abhijit; Sharma, Surbhi; Papakonstantinou, Pagona
- The Journal of Physical Chemistry C, Vol. 115, Issue 34
Membrane Insertion and Phospholipids Extraction by Graphyne Nanosheets
journal, January 2017
- Gu, Zonglin; Yang, Zaixing; Luan, Binquan
- The Journal of Physical Chemistry C, Vol. 121, Issue 4
Requirement of α and β subunit transmembrane helix separation for integrin outside-in signaling
journal, October 2007
- Zhu, Jieqing; Carman, Christopher V.; Kim, Minsoo
- Blood, Vol. 110, Issue 7
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems
journal, June 1993
- Darden, Tom; York, Darrin; Pedersen, Lee
- The Journal of Chemical Physics, Vol. 98, Issue 12
Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy
journal, January 2008
- Liu, Z.; Davis, C.; Cai, W.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 5
Computational approaches to cell–nanomaterial interactions: keeping balance between therapeutic efficiency and cytotoxicity
journal, January 2018
- Ding, Hong-ming; Ma, Yu-qiang
- Nanoscale Horizons, Vol. 3, Issue 1
Molecular Modeling for Nanomaterial–Biology Interactions: Opportunities, Challenges, and Perspectives
journal, October 2019
- Casalini, Tommaso; Limongelli, Vittorio; Schmutz, Mélanie
- Frontiers in Bioengineering and Biotechnology, Vol. 7
Understanding the pH-Dependent Behavior of Graphene Oxide Aqueous Solutions: A Comparative Experimental and Molecular Dynamics Simulation Study
journal, December 2011
- Shih, Chih-Jen; Lin, Shangchao; Sharma, Richa
- Langmuir, Vol. 28, Issue 1
Stability of Ligands on Nanoparticles Regulating the Integrity of Biological Membranes at the Nano–Lipid Interface
journal, July 2019
- Wang, Liming; Quan, Peiyu; Chen, Serena H.
- ACS Nano, Vol. 13, Issue 8
An interaction between v 8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain
journal, September 2005
- McCarty, J. H.; Cook, A. A.; Hynes, R. O.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 38
Theory, simulations and the design of functionalized nanoparticles for biomedical applications: A Soft Matter Perspective
journal, November 2017
- Angioletti-Uberti, Stefano
- npj Computational Materials, Vol. 3, Issue 1
Integrin extension enables ultrasensitive regulation by cytoskeletal force
journal, April 2017
- Li, Jing; Springer, Timothy A.
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 18
The Structure of a Receptor with Two Associating Transmembrane Domains on the Cell Surface: Integrin αIIbβ3
journal, April 2009
- Zhu, Jieqing; Luo, Bing-Hao; Barth, Patrick
- Molecular Cell, Vol. 34, Issue 2
Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb
journal, November 1991
- O'Toole, T.; Mandelman, D.; Forsyth, J.
- Science, Vol. 254, Issue 5033
Molecular dynamics simulations of biomolecules
journal, September 2002
- Karplus, Martin; McCammon, J. Andrew
- Nature Structural Biology, Vol. 9, Issue 9
A Strategy for Producing Pure Single-Layer Graphene Sheets Based on a Confined Self-Assembly Approach
journal, July 2009
- Zhang, Weixia; Cui, Jiecheng; Tao, Cheng-an
- Angewandte Chemie International Edition, Vol. 48, Issue 32
Chemistry and Properties of Nanocrystals of Different Shapes
journal, April 2005
- Burda, Clemens; Chen, Xiaobo; Narayanan, Radha
- Chemical Reviews, Vol. 105, Issue 4
Strategies in the design of nanoparticles for therapeutic applications
journal, July 2010
- Petros, Robby A.; DeSimone, Joseph M.
- Nature Reviews Drug Discovery, Vol. 9, Issue 8
Defect-assisted protein HP35 denaturation on graphene
journal, January 2019
- Gu, Zonglin; Song, Wei; Chen, Serena H.
- Nanoscale, Vol. 11, Issue 41
Surface Curvature Relation to Protein Adsorption for Carbon-based Nanomaterials
journal, June 2015
- Gu, Zonglin; Yang, Zaixing; Chong, Yu
- Scientific Reports, Vol. 5, Issue 1
Concentration-dependent binding of CdSe quantum dots on the SH3 domain
journal, January 2018
- Bell, David R.; Kang, Seung-Gu; Huynh, Tien
- Nanoscale, Vol. 10, Issue 1
Calculation of helix packing angles in protein structures
journal, July 2003
- Dalton, J. A. R.; Michalopoulos, I.; Westhead, D. R.
- Bioinformatics, Vol. 19, Issue 10
Integrin αIIbβ3 Transmembrane Domain Separation Mediates Bi-Directional Signaling across the Plasma Membrane
journal, January 2015
- Hu, Ping; Luo, Bing-Hao
- PLOS ONE, Vol. 10, Issue 1
Adsorption of Villin Headpiece onto Graphene, Carbon Nanotube, and C60: Effect of Contacting Surface Curvatures on Binding Affinity
journal, November 2011
- Zuo, Guanghong; Zhou, Xin; Huang, Qing
- The Journal of Physical Chemistry C, Vol. 115, Issue 47
Integrin signalling and function in immune cells: Integrins in immune cells
journal, March 2012
- Zhang, Yanbo; Wang, Hongyan
- Immunology, Vol. 135, Issue 4
Mechanical measurement of red cell membrane thickness
journal, April 1983
- Hochmuth, R.; Evans, C.; Wiles, H.
- Science, Vol. 220, Issue 4592
VMD: Visual molecular dynamics
journal, February 1996
- Humphrey, William; Dalke, Andrew; Schulten, Klaus
- Journal of Molecular Graphics, Vol. 14, Issue 1
Localized Lipid Packing of Transmembrane Domains Impedes Integrin Clustering
journal, March 2013
- Mehrbod, Mehrdad; Mofrad, Mohammad R. K.
- PLoS Computational Biology, Vol. 9, Issue 3