Graphene-extracted membrane lipids facilitate the activation of integrin αvβ8

Chen, Serena; Perez-Aguilar, Jose Manuel; Zhou, Ruhong

doi:10.1039/C9NR10469K

Title: Graphene-extracted membrane lipids facilitate the activation of integrin α_vβ₈

Journal Article · Sun Mar 01 00:00:00 EST 2020 · Nanoscale

DOI:https://doi.org/10.1039/C9NR10469K· OSTI ID:1615781

^[1]; Perez-Aguilar, Jose Manuel ^[2]; Zhou, Ruhong ^[3]

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)

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.

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Research Organization:: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; W. M. Keck Foundation; IBM Blue Gene Science Program

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1615781

Journal Information:: Nanoscale, Vol. 12, Issue 14; ISSN 2040-3364

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 11 works

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References (68)

Structural Basis of Integrin Activation by Talin Wegener, Kate L.; Partridge, Anthony W.; Han, Jaewon Cell, Vol. 128, Issue 1 https://doi.org/10.1016/j.cell.2006.10.048	journal	January 2007
Bilayer Thickness and Membrane Protein Function: An Energetic Perspective Andersen, Olaf S.; Koeppe, Roger E. Annual Review of Biophysics and Biomolecular Structure, Vol. 36, Issue 1 https://doi.org/10.1146/annurev.biophys.36.040306.132643	journal	June 2007
Understanding biophysicochemical interactions at the nano–bio interface Nel, Andre E.; Mädler, Lutz; Velegol, Darrell Nature Materials, Vol. 8, Issue 7 https://doi.org/10.1038/nmat2442	journal	June 2009
Breaking the Integrin Hinge: A DEFINED STRUCTURAL CONSTRAINT REGULATES INTEGRIN SIGNALING Hughes, Paul E.; Diaz-Gonzalez, Federico; Leong, Lilley Journal of Biological Chemistry, Vol. 271, Issue 12 https://doi.org/10.1074/jbc.271.12.6571	journal	March 1996
How lipids affect the activities of integral membrane proteins Lee, Anthony G. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1666, Issue 1-2 https://doi.org/10.1016/j.bbamem.2004.05.012	journal	November 2004
Scalable molecular dynamics with NAMD Phillips, James C.; Braun, Rosemary; Wang, Wei Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802 https://doi.org/10.1002/jcc.20289	journal	January 2005
Nanoparticle-mediated cellular response is size-dependent Jiang, Wen; Kim, Betty Y. S.; Rutka, James T. Nature Nanotechnology, Vol. 3, Issue 3 https://doi.org/10.1038/nnano.2008.30	journal	March 2008
Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets Tu, Yusong; Lv, Min; Xiu, Peng Nature Nanotechnology, Vol. 8, Issue 8 https://doi.org/10.1038/nnano.2013.125	journal	July 2013
Synthesis of graphene Bhuyan, Md. Sajibul Alam; Uddin, Md. Nizam; Islam, Md. Maksudul International Nano Letters, Vol. 6, Issue 2 https://doi.org/10.1007/s40089-015-0176-1	journal	February 2016
Comprehensive analysis of sequences of a protein switch: Analysis of Sequences of a Protein Switch Chen, Szu-Hua; Meller, Jaroslaw; Elber, Ron Protein Science, Vol. 25, Issue 1 https://doi.org/10.1002/pro.2723	journal	July 2015
PEGylated graphene oxide elicits strong immunological responses despite surface passivation Luo, Nana; Weber, Jeffrey K.; Wang, Shuang Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms14537	journal	February 2017
Integrins in immunity Evans, R.; Patzak, I.; Svensson, L. Journal of Cell Science, Vol. 122, Issue 2 https://doi.org/10.1242/jcs.019117	journal	December 2008
Phospholipid Membrane Fluidity Alters Ligand Binding Activity of a G Protein-Coupled Receptor by Shifting the Conformational Equilibrium Yoshida, Kouhei; Nagatoishi, Satoru; Kuroda, Daisuke Biochemistry, Vol. 58, Issue 6 https://doi.org/10.1021/acs.biochem.8b01194	journal	December 2018
Computational close up on protein-protein interactions: how to unravel the invisible using molecular dynamics simulations?: Computational close up on protein-protein interactions Rakers, Christin; Bermudez, Marcel; Keller, Bettina G. Wiley Interdisciplinary Reviews: Computational Molecular Science, Vol. 5, Issue 5 https://doi.org/10.1002/wcms.1222	journal	July 2015
The final steps of integrin activation: the end game Shattil, Sanford J.; Kim, Chungho; Ginsberg, Mark H. Nature Reviews Molecular Cell Biology, Vol. 11, Issue 4 https://doi.org/10.1038/nrm2871	journal	April 2010
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
A Specific Interface between Integrin Transmembrane Helices and Affinity for Ligand Luo, Bing-Hao; Springer, Timothy A.; Takagi, Junichi PLoS Biology, Vol. 2, Issue 6 https://doi.org/10.1371/journal.pbio.0020153	journal	June 2004
Integrin activation by talin, kindlin and mechanical forces Sun, Zhiqi; Costell, Mercedes; Fässler, Reinhard Nature Cell Biology, Vol. 21, Issue 1 https://doi.org/10.1038/s41556-018-0234-9	journal	January 2019
Surface Polyethylene Glycol Conformation Influences the Protein Corona of Polyethylene Glycol-Modified Single-Walled Carbon Nanotubes: Potential Implications on Biological Performance Sacchetti, Cristiano; Motamedchaboki, Khatereh; Magrini, Andrea ACS Nano, Vol. 7, Issue 3 https://doi.org/10.1021/nn400409h	journal	February 2013
Biomolecular Modeling: Goals, Problems, Perspectives van Gunsteren, Wilfred F.; Bakowies, Dirk; Baron, Riccardo Angewandte Chemie International Edition, Vol. 45, Issue 25 https://doi.org/10.1002/anie.200502655	journal	June 2006
Nonequilibrium Equality for Free Energy Differences Jarzynski, C. Physical Review Letters, Vol. 78, Issue 14 https://doi.org/10.1103/PhysRevLett.78.2690	journal	April 1997
Hydrogen Bond Networks in Graphene Oxide Composite Paper: Structure and Mechanical Properties Medhekar, Nikhil V.; Ramasubramaniam, Ashwin; Ruoff, Rodney S. ACS Nano, Vol. 4, Issue 4 https://doi.org/10.1021/nn901934u	journal	March 2010
The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation Calderwood, David A.; Zent, Roy; Grant, Richard Journal of Biological Chemistry, Vol. 274, Issue 40 https://doi.org/10.1074/jbc.274.40.28071	journal	October 1999
Lipid fluidity and membrane protein dynamics Lenaz, Giorgio Bioscience Reports, Vol. 7, Issue 11 https://doi.org/10.1007/BF01119473	journal	November 1987
OPM database and PPM web server: resources for positioning of proteins in membranes Lomize, Mikhail A.; Pogozheva, Irina D.; Joo, Hyeon Nucleic Acids Research, Vol. 40, Issue D1 https://doi.org/10.1093/nar/gkr703	journal	September 2011
The structure of the integrin αIIbβ3 transmembrane complex explains integrin transmembrane signalling Lau, Tong-Lay; Kim, Chungho; Ginsberg, Mark H. The EMBO Journal, Vol. 28, Issue 9 https://doi.org/10.1038/emboj.2009.63	journal	March 2009
Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins Kim, M. Science, Vol. 301, Issue 5640 https://doi.org/10.1126/science.1084174	journal	September 2003
Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo The Journal of Physical Chemistry B, Vol. 114, Issue 23 https://doi.org/10.1021/jp101759q	journal	June 2010
Biomolecular Simulation: A Computational Microscope for Molecular Biology Dror, Ron O.; Dirks, Robert M.; Grossman, J. P. Annual Review of Biophysics, Vol. 41, Issue 1 https://doi.org/10.1146/annurev-biophys-042910-155245	journal	June 2012
A Structural Mechanism of Integrin αIIbβ3 “Inside-Out” Activation as Regulated by Its Cytoplasmic Face Vinogradova, Olga; Velyvis, Algirdas; Velyviene, Asta Cell, Vol. 110, Issue 5 https://doi.org/10.1016/S0092-8674(02)00906-6	journal	September 2002
Empirical force fields for biological macromolecules: Overview and issues Mackerell, Alexander D. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20082	journal	January 2004
Structure of Graphite Oxide Revisited ^‖ Lerf, Anton; He, Heyong; Forster, Michael The Journal of Physical Chemistry B, Vol. 102, Issue 23 https://doi.org/10.1021/jp9731821	journal	June 1998
Revisiting Hydrophobic Mismatch with Free Energy Simulation Studies of Transmembrane Helix Tilt and Rotation Kim, Taehoon; Im, Wonpil Biophysical Journal, Vol. 99, Issue 1 https://doi.org/10.1016/j.bpj.2010.04.015	journal	July 2010
Multiscale simulations suggest a mechanism for integrin inside-out activation Kalli, A. C.; Campbell, I. D.; Sansom, M. S. P. Proceedings of the National Academy of Sciences, Vol. 108, Issue 29 https://doi.org/10.1073/pnas.1104505108	journal	July 2011
Integrin Mechano-chemical Signaling Generates Plasma Membrane Nanodomains that Promote Cell Spreading Kalappurakkal, Joseph Mathew; Anilkumar, Anupama Ambika; Patra, Chandrima Cell, Vol. 177, Issue 7 https://doi.org/10.1016/j.cell.2019.04.037	journal	June 2019
Charging nanoparticles: increased binding of Gd@C ₈₂ (OH) ₂₂ derivatives to human MMP-9 Chen, Serena H.; Kang, Seung-gu; Luo, Judong Nanoscale, Vol. 10, Issue 12 https://doi.org/10.1039/C8NR00127H	journal	January 2018
Interfacing proteins with graphitic nanomaterials: from spontaneous attraction to tailored assemblies De Leo, Federica; Magistrato, Alessandra; Bonifazi, Davide Chemical Society Reviews, Vol. 44, Issue 19 https://doi.org/10.1039/C5CS00190K	journal	January 2015
Atomic Structure of Reduced Graphene Oxide Gómez-Navarro, Cristina; Meyer, Jannik C.; Sundaram, Ravi S. Nano Letters, Vol. 10, Issue 4 https://doi.org/10.1021/nl9031617	journal	April 2010
Biopharmaceutics and Therapeutic Potential of Engineered Nanomaterials Liang, Xing-Jie; Chen, Chunying; Zhao, Yuliang Current Drug Metabolism, Vol. 9, Issue 8 https://doi.org/10.2174/138920008786049230	journal	October 2008
The energy landscape of a protein switch Chen, Szu-Hua; Elber, Ron Physical Chemistry Chemical Physics, Vol. 16, Issue 14 https://doi.org/10.1039/c3cp55209h	journal	January 2014
Probing the Thermal Deoxygenation of Graphene Oxide Using High-Resolution In Situ X-ray-Based Spectroscopies Ganguly, Abhijit; Sharma, Surbhi; Papakonstantinou, Pagona The Journal of Physical Chemistry C, Vol. 115, Issue 34 https://doi.org/10.1021/jp203741y	journal	August 2011
Membrane Insertion and Phospholipids Extraction by Graphyne Nanosheets Gu, Zonglin; Yang, Zaixing; Luan, Binquan The Journal of Physical Chemistry C, Vol. 121, Issue 4 https://doi.org/10.1021/acs.jpcc.6b10548	journal	January 2017
Requirement of α and β subunit transmembrane helix separation for integrin outside-in signaling Zhu, Jieqing; Carman, Christopher V.; Kim, Minsoo Blood, Vol. 110, Issue 7 https://doi.org/10.1182/blood-2007-03-080077	journal	October 2007
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems Darden, Tom; York, Darrin; Pedersen, Lee The Journal of Chemical Physics, Vol. 98, Issue 12 https://doi.org/10.1063/1.464397	journal	June 1993
Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy Liu, Z.; Davis, C.; Cai, W. Proceedings of the National Academy of Sciences, Vol. 105, Issue 5 https://doi.org/10.1073/pnas.0707654105	journal	January 2008
Computational approaches to cell–nanomaterial interactions: keeping balance between therapeutic efficiency and cytotoxicity Ding, Hong-ming; Ma, Yu-qiang Nanoscale Horizons, Vol. 3, Issue 1 https://doi.org/10.1039/C7NH00138J	journal	January 2018
Molecular Modeling for Nanomaterial–Biology Interactions: Opportunities, Challenges, and Perspectives Casalini, Tommaso; Limongelli, Vittorio; Schmutz, Mélanie Frontiers in Bioengineering and Biotechnology, Vol. 7 https://doi.org/10.3389/fbioe.2019.00268	journal	October 2019
Understanding the pH-Dependent Behavior of Graphene Oxide Aqueous Solutions: A Comparative Experimental and Molecular Dynamics Simulation Study Shih, Chih-Jen; Lin, Shangchao; Sharma, Richa Langmuir, Vol. 28, Issue 1 https://doi.org/10.1021/la203607w	journal	December 2011
Stability of Ligands on Nanoparticles Regulating the Integrity of Biological Membranes at the Nano–Lipid Interface Wang, Liming; Quan, Peiyu; Chen, Serena H. ACS Nano, Vol. 13, Issue 8 https://doi.org/10.1021/acsnano.9b00114	journal	July 2019
An interaction between v 8 integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain McCarty, J. H.; Cook, A. A.; Hynes, R. O. Proceedings of the National Academy of Sciences, Vol. 102, Issue 38 https://doi.org/10.1073/pnas.0506068102	journal	September 2005
Theory, simulations and the design of functionalized nanoparticles for biomedical applications: A Soft Matter Perspective Angioletti-Uberti, Stefano npj Computational Materials, Vol. 3, Issue 1 https://doi.org/10.1038/s41524-017-0050-y	journal	November 2017
Integrin extension enables ultrasensitive regulation by cytoskeletal force Li, Jing; Springer, Timothy A. Proceedings of the National Academy of Sciences, Vol. 114, Issue 18 https://doi.org/10.1073/pnas.1704171114	journal	April 2017
The Structure of a Receptor with Two Associating Transmembrane Domains on the Cell Surface: Integrin αIIbβ3 Zhu, Jieqing; Luo, Bing-Hao; Barth, Patrick Molecular Cell, Vol. 34, Issue 2 https://doi.org/10.1016/j.molcel.2009.02.022	journal	April 2009
Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb O'Toole, T.; Mandelman, D.; Forsyth, J. Science, Vol. 254, Issue 5033 https://doi.org/10.1126/science.1948065	journal	November 1991
Molecular dynamics simulations of biomolecules Karplus, Martin; McCammon, J. Andrew Nature Structural Biology, Vol. 9, Issue 9 https://doi.org/10.1038/nsb0902-646	journal	September 2002
A Strategy for Producing Pure Single-Layer Graphene Sheets Based on a Confined Self-Assembly Approach Zhang, Weixia; Cui, Jiecheng; Tao, Cheng-an Angewandte Chemie International Edition, Vol. 48, Issue 32 https://doi.org/10.1002/anie.200902365	journal	July 2009
Chemistry and Properties of Nanocrystals of Different Shapes Burda, Clemens; Chen, Xiaobo; Narayanan, Radha Chemical Reviews, Vol. 105, Issue 4 https://doi.org/10.1021/cr030063a	journal	April 2005
Strategies in the design of nanoparticles for therapeutic applications Petros, Robby A.; DeSimone, Joseph M. Nature Reviews Drug Discovery, Vol. 9, Issue 8 https://doi.org/10.1038/nrd2591	journal	July 2010
Defect-assisted protein HP35 denaturation on graphene Gu, Zonglin; Song, Wei; Chen, Serena H. Nanoscale, Vol. 11, Issue 41 https://doi.org/10.1039/C9NR01143A	journal	January 2019
Surface Curvature Relation to Protein Adsorption for Carbon-based Nanomaterials Gu, Zonglin; Yang, Zaixing; Chong, Yu Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep10886	journal	June 2015
Concentration-dependent binding of CdSe quantum dots on the SH3 domain Bell, David R.; Kang, Seung-Gu; Huynh, Tien Nanoscale, Vol. 10, Issue 1 https://doi.org/10.1039/C7NR06148J	journal	January 2018
Calculation of helix packing angles in protein structures Dalton, J. A. R.; Michalopoulos, I.; Westhead, D. R. Bioinformatics, Vol. 19, Issue 10 https://doi.org/10.1093/bioinformatics/btg141	journal	July 2003
Integrin αIIbβ3 Transmembrane Domain Separation Mediates Bi-Directional Signaling across the Plasma Membrane Hu, Ping; Luo, Bing-Hao PLOS ONE, Vol. 10, Issue 1 https://doi.org/10.1371/journal.pone.0116208	journal	January 2015
Adsorption of Villin Headpiece onto Graphene, Carbon Nanotube, and C60: Effect of Contacting Surface Curvatures on Binding Affinity Zuo, Guanghong; Zhou, Xin; Huang, Qing The Journal of Physical Chemistry C, Vol. 115, Issue 47 https://doi.org/10.1021/jp208967t	journal	November 2011
Integrin signalling and function in immune cells: Integrins in immune cells Zhang, Yanbo; Wang, Hongyan Immunology, Vol. 135, Issue 4 https://doi.org/10.1111/j.1365-2567.2011.03549.x	journal	March 2012
Mechanical measurement of red cell membrane thickness Hochmuth, R.; Evans, C.; Wiles, H. Science, Vol. 220, Issue 4592 https://doi.org/10.1126/science.6828875	journal	April 1983
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Localized Lipid Packing of Transmembrane Domains Impedes Integrin Clustering Mehrbod, Mehrdad; Mofrad, Mohammad R. K. PLoS Computational Biology, Vol. 9, Issue 3 https://doi.org/10.1371/journal.pcbi.1002948	journal	March 2013

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Title: Graphene-extracted membrane lipids facilitate the activation of integrin α_vβ₈