Cell adhesion and polarisation on molecularly defined spacing gradient surfaces of cyclic RGDfK peptide patches
Cell adhesion and polarisation on molecularly defined spacing gradient surfaces of cyclic RGDfK peptide patches
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DOI：
10.1016/j.ejcb.2008.03.011
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发表时间：
2008-09-01
影响因子：
6.6
通讯作者：
Spatz, Joachim P.
中科院分区：
文献类型：
--
作者：
Hirschfeld-Warneken, Vera C.;Arnold, Marco;Spatz, Joachim P.
体内细胞迁移和定位由可溶性和结合的化学梯度协调地引导。在这里，细胞外基质分子的梯度通过称为嵌段共聚物纳米光刻（BCN）的表面纳米图案化技术和生物功能化技术的组合合成形成。BCN的改良底物浸涂工艺允许在界面处形成精确的分子梯度的环状RGDfK肽补丁，其被呈递给细胞用于测试细胞粘附和极化。由BCN形成的表面由具有颗粒间距梯度的六方有序的金点图案组成。每个点作为结合环状RGDfK肽的化学锚，其被α（v）β（3）整联蛋白特异性识别。由于空间位阻，只有一个整联蛋白的Lip与一个功能化的金点结合，形成肽补丁间隔。我们展示了细胞形态，粘附面积，肌动蛋白和黏着斑蛋白分布以及细胞体极化是如何受到肽补丁间距梯度的影响。因此，当梯度强度至少为15 nm/mm时，这些粘附配体的梯度诱导细胞朝向更小的颗粒间距取向。这意味着贴壁细胞在整个细胞体上区分配体斑块间距的敏感性约为1 nm。(C)2008年Elsevier GmbH。All rights reserved.
In vivo cell migration and location are orchestrally guided by soluble and bound chemical gradients. Here, gradients of extracellular matrix molecules are formed synthetically by the combination Of a Surface nanopatterning technique called block copolymer nanolithography (BCN) and a biofunctionalisation technique. A modified Substrate dip-coating process of BCN allows for the Formation of precise molecular gradients of cyclic RGDfK peptide patches at interfaces, which are presented to cells for testing cell adhesion and polarisation. Surfaces formed by BCN consist of hexagonally ordered gold dot patterns with a gradient in particle spacing. Each dot serves as a chemical anchor for the binding of cyclic RGDfK peptides, which are specifically recognised by alpha(v)beta(3) integrins. Due to steric hindrance Only Lip to one integrin binds to one functionalised gold dot which forms a peptide patch spacing. We demonstrate how cell morphology, adhesion area, actin and vinculin distribution as well as cell body polarisation are influenced by the peptide patch spacing gradient. As a consequence, these gradients of adhesive ligands induce cell orientation towards smaller particle spacing when the gradient strength is 15 nm/mm at least. This implicates that an adherent cell's sensitivity to differentiate between ligand patch spacing is approximately 1 nm across the cell body. (C) 2008 Elsevier GmbH. All rights reserved.