School of Engineering, University of Warwick, Coventry, United Kingdom.
School of Cardiovascular Medicine & Sciences, King's British Heart Foundation Centre of Research Excellence, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
Biochim Biophys Acta Mol Cell Res. 2021 Apr;1868(5):118972. doi: 10.1016/j.bbamcr.2021.118972. Epub 2021 Jan 27.
Dermal fibroblasts play a key role in maintaining homoeostasis and functionality of the skin. Their contractility plays a role in changes observed during ageing, especially in processes such as wound healing, inflammation, wrinkling and scar tissue formation as well as structural changes on extracellular matrix. Although alternations in skin physiology and morphology have been previously described, there remains a paucity of information about the influence of chronological ageing on dermal fibroblast contractility. In this study, we applied a novel nano-biomechanical technique on cell-embedded collagen hydrogels in combination with mathematical modelling and numerical simulation to measure contraction forces of normal human dermal fibroblasts (NHDF). We achieved quantitative differentiation of the contractility of cells derived from 'young' (< 30 years old) and 'aged' (> 60 years old) donors. Transforming growth factor β1 (TGF-β1) was used to stimulate the fibroblasts to assess their contractile potential. NHDF from aged donors exhibited a greater basal contractile force, while in contrast, NHDF from young donors have shown a significantly larger contractile force in response to TGF-β1 treatment. These findings validate our nano-biomechanical measurement technique and provide new insights for considering NHDF contractility in regenerative medicine and as a biomarker of dermal ageing processes.
皮肤成纤维细胞在维持皮肤的内稳态和功能方面发挥着关键作用。它们的收缩性在衰老过程中所观察到的变化中起着作用,特别是在伤口愈合、炎症、皱纹和疤痕组织形成以及细胞外基质结构变化等过程中。尽管先前已经描述了皮肤生理学和形态学的改变,但关于年龄增长对皮肤成纤维细胞收缩性的影响,信息仍然匮乏。在这项研究中,我们应用了一种新型的纳米生物力学技术,将其应用于细胞嵌入的胶原水凝胶中,结合数学建模和数值模拟,来测量正常人类皮肤成纤维细胞(NHDF)的收缩力。我们实现了对来自“年轻”(<30 岁)和“年老”(>60 岁)供体的细胞收缩性的定量区分。转化生长因子 β1(TGF-β1)被用于刺激成纤维细胞,以评估它们的收缩潜力。与年轻供体的 NHDF 相比,年老供体的 NHDF 表现出更大的基础收缩力,而年轻供体的 NHDF 在 TGF-β1 处理下表现出显著更大的收缩力。这些发现验证了我们的纳米生物力学测量技术,并为考虑 NHDF 收缩性在再生医学中的应用以及作为皮肤老化过程的生物标志物提供了新的见解。