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用于研究整合素介导黏附的最小合成细胞。

Minimal synthetic cells to study integrin-mediated adhesion.

作者信息

Frohnmayer Johannes P, Brüggemann Dorothea, Eberhard Christian, Neubauer Stefanie, Mollenhauer Christine, Boehm Heike, Kessler Horst, Geiger Benjamin, Spatz Joachim P

机构信息

Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, 70569 Stuttgart (Germany).

Department of Biophysical Chemistry, University of Heidelberg, INF 253, 69120 Heidelberg (Germany).

出版信息

Angew Chem Int Ed Engl. 2015 Oct 12;54(42):12472-8. doi: 10.1002/anie.201503184. Epub 2015 Aug 7.

Abstract

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 αIIb β3 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 αIIb β3 .

摘要

为了阐明细胞粘附相关的分子途径,合成细胞提供了一个独特的优势,即拥有一个分子复杂性降低且可控的模型系统。在此,我们表明,以重组血小板整合素αIIbβ3作为介导粘附的跨膜蛋白的脂质体,是用于研究特定环境中细胞粘附机制的功能性最小细胞模型。使用具有耗散监测功能的石英晶体微天平分析了这些合成细胞与各种细胞外基质蛋白的相互作用。数据表明,整合素在功能上被整合到脂质囊泡中,从而使工程化脂质体能够特异性地粘附到纤维蛋白原和纤连蛋白功能化的表面。然后,在肽GRGDSP存在的情况下,我们能够引发整合素脂质体从这些表面脱离,而使用我们新合成的特异性抑制整合素αIIbβ3的肽模拟物SN529时,这一过程甚至更快。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75b1/4675076/0245d757f4ee/anie0054-12472-f1.jpg

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