Department of Electronics and Communications Engineering, Tampere University of Technology, BioMediTech , Finn-Medi 1 L 4, Biokatu 6, FI-33520 Tampere, Finland.
Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zurich , CH-8092 Zurich, Switzerland.
ACS Nano. 2017 Apr 25;11(4):3867-3874. doi: 10.1021/acsnano.7b00161. Epub 2017 Mar 22.
Biomimetic and stimuli-responsive cell-material interfaces are actively being developed to study and control various cell-dynamics phenomena. Since cells naturally reside in the highly dynamic and complex environment of the extracellular matrix, attempts are being made to replicate these conditions in synthetic biomaterials. Supramolecular chemistry, dealing with noncovalent interactions, has recently provided possibilities to incorporate such dynamicity and responsiveness in various types of architectures. Using a cucurbit[8]uril-based host-guest system, we have successfully established a dynamic and electrochemically responsive interface for the display of the integrin-specific ligand, Arg-Gly-Asp (RGD), to promote cell adhesion. Due to the weak nature of the noncovalent forces by which the components at the interface are held together, we expected that cell adhesion would also be weaker in comparison to traditional interfaces where ligands are usually immobilized by covalent linkages. To assess the stability and limitations of our noncovalent interfaces, we performed single-cell force spectroscopy studies using fluid force microscopy. This technique enabled us to measure rupture forces of multiple cells that were allowed to adhere for several hours on individual substrates. We found that the rupture forces of cells adhered to both the noncovalent and covalent interfaces were nearly identical for up to several hours. We have analyzed and elucidated the reasons behind this result as a combination of factors including the weak rupture force between linear Arg-Gly-Asp and integrin, high surface density of the ligand, and increase in effective concentration of the supramolecular components under spread cells. These characteristics enable the construction of highly dynamic biointerfaces without compromising cell-adhesive properties.
仿生和刺激响应的细胞-材料界面正在被积极开发，以研究和控制各种细胞动力学现象。由于细胞天然存在于细胞外基质的高度动态和复杂环境中，因此正在尝试在合成生物材料中复制这些条件。超分子化学处理非共价相互作用，最近为在各种类型的结构中纳入这种动态性和响应性提供了可能性。使用基于葫芦[8]脲的主客体体系，我们成功地建立了一个动态和电化学响应的界面，用于展示整合素特异性配体精氨酸-甘氨酸-天冬氨酸（RGD），以促进细胞黏附。由于界面上的组件通过非共价力结合在一起，因此我们预计与传统界面相比，细胞黏附也会较弱，在传统界面中，配体通常通过共价键固定。为了评估我们的非共价界面的稳定性和局限性，我们使用流体力显微镜进行了单细胞力谱研究。这项技术使我们能够测量多个细胞的断裂力，这些细胞在单个底物上允许黏附几个小时。我们发现，黏附在非共价和共价界面上的细胞的断裂力在长达几个小时的时间内几乎相同。我们已经分析并阐明了这一结果的原因，这是多种因素的结合，包括线性精氨酸-甘氨酸-天冬氨酸和整合素之间的弱断裂力、配体的高表面密度以及在展开细胞下超分子成分的有效浓度增加。这些特性使我们能够构建高度动态的生物界面，而不会损害细胞黏附特性。
