title: A molecular toolkit for the functionalization of titanium-based biomaterials that selectively control integrin-mediated cell adhesion.
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.
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Rechenmacher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Neubauer
authors.forename: Carlos
authors.initials: C
authors.lastname: Mas-Moruno
authors.forename: Petra M
authors.initials: PM
authors.lastname: Dorfner
authors.forename: Julien
authors.initials: J
authors.lastname: Polleux
authors.forename: Judith
authors.initials: J
authors.lastname: Guasch
authors.forename: Bert
authors.initials: B
authors.lastname: Conings
authors.forename: Hans-Gerd
authors.initials: HG
authors.lastname: Boyen
authors.forename: Alexander
authors.initials: A
authors.lastname: Bochen
authors.forename: Tariq R
authors.initials: TR
authors.lastname: Sobahi
authors.forename: Rainer
authors.initials: R
authors.lastname: Burgkart
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Spatz
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002448:Cell Adhesion; D057930:Click Chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry* / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D057786:Peptidomimetics / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D014025:Titanium
chemical_list: D001672:Biocompatible Materials; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D057786:Peptidomimetics; C047981:arginyl-glycyl-aspartic acid; D014025:Titanium
keywords: biomaterials; cell adhesion; click chemistry; integrins; peptidomimetics; surface coating; titanium