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Minimal Synthetic Cells to Study Integrin-Mediated Adhesion

Year: 2015

Journal: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol. 54, p 12472-12478, 20160201

Authors: Frohnmayer, Johannes P.; Brueggemann, Dorothea; Eberhard, Christian; Neubauer, Stefanie; Mollenhauer, Christine; Boehm, Heike; Kessler, Horst; Geiger, Benjamin; Spatz, Joachim P.

Organizations: Max Planck Inst Intelligent Syst, Dept New Mat & Biosyst, D-70569 Stuttgart, Germany; Heidelberg Univ, Dept Biophys Chem, D-69120 Heidelberg, Germany; Tech Univ Munich, Inst Adv Study, D-85747 Garching, Germany; Tech Univ Munich, Dept Chem, Ctr Integrated Prot Sci CIPSM, D-85747 Garching, Germany; Max Planck Inst Intelligent Syst, CSF Biomat & Cellular Biophys, D-70569 Stuttgart, Germany; Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

To shed light on cell-adhesion-related molecular pathways, synthetic cells offer the unique advantage of a well-controlled model system with reduced molecular complexity. Herein, we show that liposomes with the reconstituted platelet integrin alpha(IIb)beta(3) as the adhesion-mediating transmembrane protein are a functional minimal cell model for studying cellular adhesion mechanisms in a defined environment. The interaction of these synthetic cells with various extracellular matrix proteins was analyzed using a quartz crystal microbalance with dissipation monitoring. The data indicated that integrin was functionally incorporated into the lipid vesicles, thus enabling integrin-specific adhesion of the engineered liposomes to fibrinogen-and fibronectin-functionalized surfaces. Then, we were able to initiate the detachment of integrin liposomes from these surfaces in the presence of the peptide GRGDSP, a process that is even faster with our newly synthesized peptide mimetic SN529, which specifically inhibits the integrin alpha(IIb)beta(3).