The Nano-Scale Mechanical Properties of the Extracellular Matrix Regulate Dermal Fibroblast Function
The Nano-Scale Mechanical Properties of the Extracellular Matrix Regulate Dermal Fibroblast Function
复制标题
DOI：
10.1038/jid.2014.90
复制
发表时间：
2014-07-01
影响因子：
6.5
通讯作者：
Hinz, Boris
中科院分区：
文献类型：
--
作者：
Achterberg, Volker F.;Buscemi, Lara;Hinz, Boris
在皮肤老化或组织重塑过程中，真皮的机械性质发生变化，并影响常驻成纤维细胞的活性。为了建立弹性培养基质，再现真皮的可变柔软度，我们确定了杨氏弹性模量E的人真皮细胞感知水平，使用原子力显微镜。真皮E值在0.1 ~ 10 kPa之间，随身体面积和真皮层的不同而不同，在26-55岁之间有随年龄增长而增加的趋势。将在“皮肤软”E（5 kPa）硅胶培养基质上培养的人真皮成纤维细胞的活化状态与硬塑料培养物（GPa）、胶原凝胶培养物（0.1-9 kPa）和新鲜人真皮组织进行比较。与胶原凝胶和塑料培养物相比，在皮肤软硅胶上培养的成纤维细胞显示纤维化相关基因的mRNA水平较低，基质金属蛋白酶（MMPs）MMP-1和MMP-3的表达增加。与任何其他测试的培养条件相比，成纤维细胞在“皮肤软”硅胶培养基质上表现出的活化特征与人真皮的活化特征最相似。因此，提供仿生机械条件产生的成纤维细胞比由刚性常规培养表面自发激活的成纤维细胞更适合于研究生理相关的细胞过程。
Changes in the mechanical properties of dermis occur during skin aging or tissue remodeling and affect the activity of resident fibroblasts. With the aim to establish elastic culture substrates that reproduce the variable softness of dermis, we determined Young's elastic modulus E of human dermis at the cell perception level using atomic force microscopy. The E of dermis ranged from 0.1 to 10 kPa, varied depending on body area and dermal layer, and tended to increase with age in 26-55-year-old donors. The activation state of human dermal fibroblasts cultured on "skin-soft" E (5 kPa) silicone culture substrates was compared with stiff plastic culture (GPa), collagen gel cultures (0.1-9 kPa), and fresh human dermal tissue. Fibroblasts cultured on skin-soft silicones displayed low mRNA levels of fibrosis-associated genes and increased expression of the matrix metalloproteinases (MMPs) MMP-1 and MMP-3 as compared with collagen gel and plastic cultures. The activation profile exhibited by fibroblasts on "skin-soft" silicone culture substrates was most comparable with that of human dermis than any other tested culture condition. Hence, providing biomimetic mechanical conditions generates fibroblasts that are more suitable to investigate physiologically relevant cell processes than fibroblasts spontaneously activated by stiff conventional culture surfaces.