Wu Dan Jing, Rutten Martin G T A, Huang Jingyi, Schotman Maaike J G, van Sprang Johnick F, Tiemeijer Bart M, Ter Huurne Gijs M, Wijnands Sjors P W, Diba Mani, Dankers Patricia Y W
Laboratory for Cell and Tissue Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, PO Box 513 ,Eindhoven MB 5600, The Netherlands.
Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513 ,Eindhoven MB 5600, The Netherlands.
Macromolecules. 2024 Jul 3;57(14):6606-6615. doi: 10.1021/acs.macromol.4c00567. eCollection 2024 Jul 23.
The cellular microenvironment is composed of a dynamic hierarchical fibrillar architecture providing a variety of physical and bioactive signals to the surrounding cells. This dynamicity, although common in biology, is a challenge to control in synthetic matrices. Here, responsive synthetic supramolecular monomers were designed that are able to assemble into hierarchical fibrous structures, combining supramolecular fiber formation via hydrogen bonding interactions, with a temperature-responsive hydrophobic collapse, resulting in cross-linking and hydrogel formation. Therefore, amphiphilic molecules were synthesized, composed of a hydrogen bonding ureido-pyrimidinone (UPy) unit, a hydrophobic alkyl spacer, and a hydrophilic oligo(ethylene glycol) tail. The temperature responsive behavior was introduced by functionalizing these supramolecular amphiphiles with a relatively short poly(-isopropylacrylamide) (PNIPAM) chain ( ∼ 2.5 or 5.5 kg/mol). To precisely control the assembly of these monomers, the length of the alkyl spacer between the UPy moiety and PNIPAM was varied in length. A robust sol-gel transition, with the dodecyl UPy-PNIPAM molecule, was obtained, with a network elasticity enhancing over 2000 times upon heating above room temperature. The UPy-PNIPAM compounds with shorter alkyl spacers were already hydrogels at room temperature. The sol-gel transition of the dodecyl UPy-PNIPAM hydrogelator could be tuned by the incorporation of different UPy-functionalized monomers. Furthermore, we demonstrated the suitability of this system for microfluidic cell encapsulation through a convenient temperature sol-gel transition. Our results indicate that this novel thermoresponsive supramolecular system offers a modular platform to study and guide single-cell behavior.
细胞微环境由动态的分级纤维结构组成，为周围细胞提供各种物理和生物活性信号。这种动态性虽然在生物学中很常见，但在合成基质中控制却是一项挑战。在此，设计了响应性合成超分子单体，它们能够组装成分级纤维结构，将通过氢键相互作用形成超分子纤维与温度响应性疏水塌陷相结合，从而导致交联和水凝胶形成。因此，合成了两亲分子，其由氢键脲基嘧啶酮（UPy）单元、疏水烷基间隔基和亲水聚乙二醇尾组成。通过用相对较短的聚（N-异丙基丙烯酰胺）（PNIPAM）链（约2.5或5.5 kg/mol）对这些超分子两亲物进行功能化引入温度响应行为。为了精确控制这些单体的组装，改变了UPy部分和PNIPAM之间烷基间隔基的长度。使用十二烷基UPy-PNIPAM分子获得了稳健的溶胶-凝胶转变，在加热到室温以上时网络弹性增强了2000倍以上。具有较短烷基间隔基的UPy-PNIPAM化合物在室温下已经是水凝胶。十二烷基UPy-PNIPAM水凝胶剂的溶胶-凝胶转变可以通过加入不同的UPy功能化单体来调节。此外，我们通过方便的温度溶胶-凝胶转变证明了该系统适用于微流控细胞封装。我们的结果表明，这种新型的热响应超分子系统提供了一个模块化平台来研究和指导单细胞行为。
