Hepburn Matt S, Wijesinghe Philip, Major Luke G, Li Jiayue, Mowla Alireza, Astell Chrissie, Park Hyun Woo, Hwang Yongsung, Choi Yu Suk, Kennedy Brendan F
BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, 6009, Australia and Centre for Medical Research, The University of Western Australia, Crawley, Western Australia, 6009, Australia.
Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, 35, Stirling Highway, Perth, Western Australia, 6009, Australia.
Biomed Opt Express. 2020 Jan 14;11(2):867-884. doi: 10.1364/BOE.383419. eCollection 2020 Feb 1.
Recent studies in mechanobiology have revealed the importance of cellular and extracellular mechanical properties in regulating cellular function in normal and disease states. Although it is established that cells should be investigated in a three-dimensional (3-D) environment, most techniques available to study mechanical properties on the microscopic scale are unable to do so. In this study, for the first time, we present volumetric images of cellular and extracellular elasticity in 3-D biomaterials using quantitative micro-elastography (QME). We achieve this by developing a novel strain estimation algorithm based on 3-D linear regression to improve QME system resolution. We show that QME can reveal elevated elasticity surrounding human adipose-derived stem cells (ASCs) embedded in soft hydrogels. We observe, for the first time in 3-D, further elevation of extracellular elasticity around ASCs with overexpressed TAZ; a mechanosensitive transcription factor which regulates cell volume. Our results demonstrate that QME has the potential to study the effects of extracellular mechanical properties on cellular functions in a 3-D micro-environment.
机械生物学领域的最新研究揭示了细胞和细胞外机械特性在调节正常和疾病状态下细胞功能方面的重要性。尽管已经确定应该在三维(3-D)环境中研究细胞,但大多数用于在微观尺度上研究机械特性的技术无法做到这一点。在本研究中,我们首次使用定量微弹性成像(QME)展示了三维生物材料中细胞和细胞外弹性的体积图像。我们通过开发一种基于三维线性回归的新型应变估计算法来提高QME系统分辨率,从而实现了这一目标。我们表明,QME可以揭示嵌入软水凝胶中的人脂肪干细胞(ASC)周围弹性的升高。我们首次在三维环境中观察到,过表达TAZ(一种调节细胞体积的机械敏感转录因子)的ASC周围细胞外弹性进一步升高。我们的结果表明,QME有潜力在三维微环境中研究细胞外机械特性对细胞功能的影响。