Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
Ann Biomed Eng. 2012 May;40(5):1061-72. doi: 10.1007/s10439-011-0483-2. Epub 2011 Dec 8.
Despite cellular environments having dynamic characteristics, many laboratories utilized static polyacrylamide hydrogels to study the ECM-cell relationship. To attain a more in vivo like environment, we have developed a dynamic, DNA-crosslinked hydrogel (DNA gel). Through the controlled delivery of DNA, we can temporally decrease or increase gel stiffness while expanding or contracting the gel, respectively. These dual mechanical changes make DNA gels a cell-ECM model for studying dynamic mechano-regulated processes, such as wound healing. Here, we characterized DNA gels on a mechanical and cellular level. In contrast to our previous publication, in which we examined the increasing stiffness effects on fibroblast morphology, we examined the effects of decreased matrix stiffness on fibroblast morphology. In addition, we quantified the bulk and/or local stress and strain properties of dynamic gels. Gels generated about 0.5 Pa stress and about 6-11% strain upon softening to generate larger and more circular fibroblasts. These results complemented our previous study, where dynamic gels contracted upon stiffening to generate smaller and longer fibroblasts. In conclusion, we developed a biomaterial that increases and decreases in stiffness while contracting and expanding, respectively. We found that the dynamic deformation directionality of the matrix determined the fibroblast morphology and possibly influences function.
尽管细胞环境具有动态特征,但许多实验室仍使用静态聚丙烯酰胺水凝胶来研究细胞外基质与细胞的关系。为了获得更接近体内环境的条件,我们开发了一种动态的、经 DNA 交联的水凝胶(DNA 凝胶)。通过 DNA 的控制释放,我们可以分别在增加或减少凝胶硬度的同时扩展或收缩凝胶。这两种机械变化使 DNA 凝胶成为研究动态机械调节过程(如伤口愈合)的细胞-细胞外基质模型。在这里,我们从机械和细胞两个层面上对 DNA 凝胶进行了表征。与我们之前的研究不同,在之前的研究中,我们研究了增加硬度对成纤维细胞形态的影响,而在本研究中,我们研究了基质硬度降低对成纤维细胞形态的影响。此外,我们还定量分析了动态凝胶的整体和/或局部应力和应变特性。当基质变软时,凝胶会产生约 0.5Pa 的应力和约 6-11%的应变,从而使成纤维细胞变得更大更圆。这些结果补充了我们之前的研究,其中动态凝胶在变硬时会收缩,从而使成纤维细胞变得更小更长。总之,我们开发了一种生物材料,它可以在收缩和扩展时分别增加和减少硬度。我们发现,基质的动态变形方向决定了成纤维细胞的形态,并且可能会影响功能。