Shu Yiwei, Chan Ho Nam, Guan Dongshi, Wu Hongkai, Ma Lan
Division of Life Science & Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.
Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China.
Sci Bull (Beijing). 2017 Feb 15;62(3):222-228. doi: 10.1016/j.scib.2016.12.012. Epub 2016 Dec 27.
In this work, we developed a simple method to fabricate a thickness-based continuous stiffness gradient for biological studies. It was made by glass slides, polydimethylsiloxane (PDMS) pre-polymer, spacer and clips only, without any sophisticated equipment. It is easy to fabricate in any general biological and pharmaceutical laboratories. The stiffness gradient was characterized in terms of apparent Young's modulus by atomic force microscopy (AFM) and the Young's modulus along the gradient was found to be 8.5-120kPa, which is within the physiological relevant range. HeLa-C3 cells were cultured on the gradient to study their morphological behavior according to the substrate stiffness. Furthermore, the drug efficiency of etoposide, an anti-cancer drug, was studied along the substrate stiffness gradient. It was found that HeLa-C3 cells cultured on the soft region of the gradient (8.5-11kPa) are more sensitive to etoposide. We believe the proposed device could promote cell investigations and drug screenings on a substrate with comparable stiffness to the native tissue.
在这项工作中，我们开发了一种简单的方法来制造用于生物学研究的基于厚度的连续刚度梯度。它仅由载玻片、聚二甲基硅氧烷（PDMS）预聚物、间隔物和夹子制成，无需任何复杂设备。在任何普通的生物学和制药实验室都易于制造。通过原子力显微镜（AFM）根据表观杨氏模量对刚度梯度进行了表征，并且发现沿梯度方向的杨氏模量为8.5 - 120kPa，这处于生理相关范围内。将HeLa - C3细胞培养在该梯度上，以根据底物刚度研究其形态行为。此外，还研究了抗癌药物依托泊苷沿底物刚度梯度的药物疗效。结果发现，在梯度软区域（8.5 - 11kPa）培养的HeLa - C3细胞对依托泊苷更敏感。我们相信所提出的装置可以促进在与天然组织具有可比刚度的底物上进行细胞研究和药物筛选。
