A Molecular Toolkit for the Functionalization of Titanium-Based Biomaterials That Selectively Control Integrin-Mediated Cell Adhesion

Authors

  • Dr. Florian Rechenmacher,

    1. Institute for Advanced Study (IAS) and Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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    • These authors contributed equally to this work.

  • Dr. Stefanie Neubauer,

    1. Institute for Advanced Study (IAS) and Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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    • These authors contributed equally to this work.

  • Dr. Carlos Mas-Moruno,

    1. Institute for Advanced Study (IAS) and Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
    2. Current address: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), Av. Diagonal 647, 08028 Barcelona (Spain)
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  • Dr. Petra M. Dorfner,

    1. Orthopedic and Trauma Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 München (Germany)
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  • Dr. Julien Polleux,

    1. Max Planck Institut für Biochemie, Department of Molecular Medicine, Am Klopferspitz 18, 82152 Martinsried (Germany)
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  • Dr. Judith Guasch,

    1. Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, 70569 Stuttgart (Germany)
    2. Department of Biophysical Chemistry, University of Heidelberg, INF 253, 69120 Heidelberg (Germany)
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  • Dr. Bert Conings,

    1. Institute for Materials Research, Wetenschapspark 1, 3590 Diepenbeek (Belgium)
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  • Prof. Dr. Hans-Gerd Boyen,

    1. Institute for Materials Research, Wetenschapspark 1, 3590 Diepenbeek (Belgium)
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  • Dr. Alexander Bochen,

    1. Institute for Advanced Study (IAS) and Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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  • Prof. Dr. Tariq R. Sobahi,

    1. Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589 (Saudi Arabia)
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  • Priv.-Doz. Dr. Rainer Burgkart,

    1. Orthopedic and Trauma Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 München (Germany)
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  • Prof. Dr. Joachim P. Spatz,

    1. Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, 70569 Stuttgart (Germany)
    2. Department of Biophysical Chemistry, University of Heidelberg, INF 253, 69120 Heidelberg (Germany)
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  • Prof. Dr. Reinhard Fässler,

    1. Max Planck Institut für Biochemie, Department of Molecular Medicine, Am Klopferspitz 18, 82152 Martinsried (Germany)
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  • Prof. Dr. Horst Kessler

    Corresponding author
    1. Institute for Advanced Study (IAS) and Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
    2. Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589 (Saudi Arabia)
    • Institute for Advanced Study (IAS) and Center for Integrated Protein Science (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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Abstract

We present a click chemistry-based molecular toolkit for the biofunctionalization of materials to selectively control integrin-mediated cell adhesion. To this end, α5β1-selective RGD peptidomimetics were covalently immobilized on Ti-based materials, and the capacity to promote the selective binding of α5β1 was evaluated using a solid-phase integrin binding assay. This functionalization strategy yielded surfaces with a nine-fold increased affinity for α5β1, in comparison to control samples, and total selectivity against the binding of the closely related integrin αvβ3. Moreover, our methodology allowed the screening of several phosphonic acid containing anchoring units to find the best spacer–anchor moiety required for establishing an efficient binding to titanium and to promote selective integrin binding. The integrin subtype specificity of these biofunctionalized surfaces was further examined in vitro by inducing selective adhesion of genetically modified fibroblasts, which express exclusively the α5β1 integrin. The versatility of our molecular toolkit was proven by shifting the cellular specificity of the materials from α5β1- to αvβ3-expressing fibroblasts by using an αvβ3-selective peptidomimetic as coating molecule. The results shown here represent the first functionalization of Ti-based materials with α5β1- or αvβ3-selective peptidomimetics that allow an unprecedented control to discriminate between α5β1- and αvβ3-mediated adhesions. The role of these two integrins in different biological events is still a matter of debate and is frequently discussed in literature. Thus, such bioactive titanium surfaces will be of great relevance for the study of integrin-mediated cell adhesion and the development of new biomaterials targeting specific cell types.

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