Influence of different ECM mimetic peptide sequences embedded in a nonfouling environment on the specific adhesion of human-skin keratinocytes and fibroblasts on deformable substrates
Influence of different ECM mimetic peptide sequences embedded in a nonfouling environment on the specific adhesion of human-skin keratinocytes and fibroblasts on deformable substrates
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DOI：
10.1002/smll.200600596
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发表时间：
2007-06-01
期刊：
影响因子：
13.3
通讯作者：
Moeller, Martin
中科院分区：
文献类型：
--
作者：
Salber, Jochen;Graeter, Stefan;Moeller, Martin
机械应力是细胞分化、增殖和一般行为的决定性因素。然而，机械力信号转导的具体信号转导机制还不完全清楚。一个基本问题是两者之间的明确区别。参与细胞粘附的不同细胞外基质（ECM）成分及其相应的信号传导途径。这里，提出了一种系统，其能够机械刺激人皮肤来源的角质形成细胞和人真皮成纤维细胞，所述角质形成细胞和人真皮成纤维细胞与固定在非相互作用但可变形的基底上的肽序列特异性相互作用。肽序列模拟纤连蛋白、层粘连蛋白和IV型胶原，ECM的三种主要组分。为了实现这一点，PDMS使用氨等离子体活化，并涂覆有星形异氰酸酯封端的聚（乙二醇）基预聚物，这导致功能性涂层，防止非特异性细胞粘附。通过用不同组合的肽序列官能化层来实现特异性细胞粘附。此外，提出了一种能够在极其限定的纳米结构中用细胞粘附肽装饰可变形基底的方法。细胞粘附分子在100 nm以下的距离和聚集已被证明对细胞粘附至关重要。因此，我们提出了一个新的工具箱，允许对结构和生物化学修饰的可变形基底上的人皮肤来源的细胞的粘附进行详细分析。
Mechanical stress is a decisive factor for the differentiation, proliferation, and general behavior of cells. However, the specific signaling of mechanotransduction is not filly understood. One basic problem is the clear distinction between. the different extracellular matrix (ECM) constituents that participate in cellular adhesion and their corresponding signaling pathways. Here, a system is proposed that enables mechanical stimulation of human-skin-derived keratinocytes and human dermal fibroblasts that specifically interact with peptide sequences immobilized on a non-interacting but deformable substrate. The peptide sequences mimic fibronectin, laminin, and collagen type TV, three major components of the ECM. To achieve this, PDMS is activated using ammonia plasma and coated with, star-shaped isocyanate-terminated poly(ethylene glycol)-based prepolymers, which results in a functional coating that prevents unspecific cell adhesion. Specific cell adhesion is achieved by functionalization of the layers with the peptide sequences in different combinations. Moreover, a method that enables the decoration of deformable substrates with cell-adhesion-peptides in extremely defined nanostructures is presented. The distance and clustering of cell adhesion molecules below 100 nm has been demonstrated to be of utmost importance for cell adhesion. Thus we present a new toolbox that allows for the detailed analysis of the adhesion of human-skin-derived cells on structurally and biochemically decorated deformable substrates.