Jeong Kyung Jae, Panitch Alyssa
Weldon School of Biomedical Engineering and School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47906, USA.
Biomacromolecules. 2009 May 11;10(5):1090-9. doi: 10.1021/bm801270k.
A systematic study is carried out to understand how physical and covalent crosslinks affect the mechanical properties of an eight-arm poly(ethyleneglycol)-based hydrogel. Heparin and heparin-binding peptide are used as a physical crosslinker, and an enzymatically cleavable peptide with a cysteine on each end serves as a covalent crosslinker. While physical crosslinks alone do not induce gelation due to the low binding affinity between heparin and heparin-binding peptide, the addition of covalent crosslinks leads to gel formation. Strikingly, the addition of the covalent crosslinks not only leads to gel formation, but also enhances the contribution from the physical crosslinks to the overall shear moduli, which are negligible in the absence of covalent crosslinks. The gels, which contain both covalent and physical crosslinks, are able to reversibly respond to external stimuli such as temperature and oscillatory shear unlike the purely covalent gel in which the moduli remain largely insensitive to such stimuli. Two explanations are provided for this striking phenomenon. First, the addition of covalent crosslinks increased the stress relaxation time of the gel enabling the physical interactions to contribute to the moduli. This is contrasted to the case of physically crosslinked material, which relaxes the stress too quickly, preventing the physical interactions from contributing to the low frequency moduli. Second, it is believed that the physical interactions within the covalent network were further enhanced by "macromolecular confinement", which favors the formation of compact conformational structures in the confined space. Quartz crystal microbalance (QCM) was used to measure the dissociation constant (K(d)) within the hydrogel and to demonstrate that the binding between heparin and heparin-binding peptide is stronger within the gel compared to that within the solution phase. Because extracellular matrix (ECM) contains both covalent and physical interactions between its constituents, and the mechanical properties of the ECM are important factors to control cell functions, the findings of this research may have important implications in various fields of tissue engineering and cell biology.
开展了一项系统性研究，以了解物理交联和共价交联如何影响基于八臂聚乙二醇的水凝胶的力学性能。肝素和肝素结合肽用作物理交联剂，两端各有一个半胱氨酸的可酶切肽用作共价交联剂。由于肝素与肝素结合肽之间的结合亲和力较低，仅物理交联不会引发凝胶化，但添加共价交联会导致凝胶形成。令人惊讶的是，共价交联的添加不仅导致凝胶形成，还增强了物理交联对整体剪切模量的贡献，而在没有共价交联的情况下，这种贡献可忽略不计。与模量对这种刺激基本不敏感的纯共价凝胶不同，同时含有共价和物理交联的凝胶能够可逆地响应温度和振荡剪切等外部刺激。针对这一显著现象提供了两种解释。首先，共价交联的添加增加了凝胶的应力松弛时间，使物理相互作用能够对模量产生贡献。这与物理交联材料的情况形成对比，物理交联材料应力松弛太快，阻止了物理相互作用对低频模量产生贡献。其次，据信共价网络内的物理相互作用通过“大分子限制”得到进一步增强，“大分子限制”有利于在受限空间内形成紧密的构象结构。使用石英晶体微天平（QCM）测量水凝胶内的解离常数（K(d)），并证明与溶液相中相比，肝素与肝素结合肽在凝胶内的结合更强。由于细胞外基质（ECM）的成分之间同时存在共价和物理相互作用，且ECM的力学性能是控制细胞功能的重要因素，本研究结果可能在组织工程和细胞生物学的各个领域具有重要意义。
