Yang Qunfeng, Jiang Nan, Xu Hongwei, Zhang Yajun, Xiong Chunyang, Huang Jianyong
Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China.
Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Biosens Bioelectron. 2021 Aug 15;186:113289. doi: 10.1016/j.bios.2021.113289. Epub 2021 Apr 30.
Cells in living organisms live in multiphysics-coupled environments. There is growing evidence indicating that both exogenous electric field (EEF) and extracellular stiffness gradient (ESG) can regulate directional movement of cells, which are known as electrotaxis and durotaxis, respectively. How single cells respond to the ubiquitous electromechanical coupling cues, however, remains mysterious. Using microfluidic chip-based methodology and finite element-based electromechanical coupling design strategies, we develope an electromechanical coupling microchip system, enabling us to quantitatively investigate polarization and directional migration governed by EEF and ESG at the single cell level. It is revealed that both of electrotaxis and durotaxis nonlinearly depend on the physiological EEF and ESG, respectively. Specific combinations of EEF and ESG can subtly modify the polarization states of single cells and thus induce hyperpolarization and depolarization. Cells can integrate electrotaxis and durotaxis in response to multi-cue microenvironments via subtle mechanisms involving cooperation and competition during cellular electrosensing and mechanosensing. The work offers a platform for quantifying migration and polarization of cells driven by electromechanical cues, which is essential not only for elucidating physiological and pathological processes like embryo development, and invasion and metastasis of cancer cells, but for manipulating cell behaviors in a controllable and programmable fashion.
活生物体中的细胞生活在多物理场耦合的环境中。越来越多的证据表明，外源性电场（EEF）和细胞外刚度梯度（ESG）都可以调节细胞的定向运动，分别称为电趋化和趋硬迁移。然而，单个细胞如何响应普遍存在的机电耦合信号仍然是个谜。利用基于微流控芯片的方法和基于有限元的机电耦合设计策略，我们开发了一种机电耦合微芯片系统，使我们能够在单细胞水平上定量研究由EEF和ESG控制的极化和定向迁移。结果表明，电趋化和趋硬迁移分别非线性地依赖于生理EEF和ESG。EEF和ESG的特定组合可以微妙地改变单个细胞的极化状态，从而诱导超极化和去极化。细胞可以通过在细胞电传感和机械传感过程中涉及合作和竞争的微妙机制，对多线索微环境做出反应，整合电趋化和趋硬迁移。这项工作提供了一个平台，用于量化由机电信号驱动的细胞迁移和极化，这不仅对于阐明诸如胚胎发育、癌细胞侵袭和转移等生理和病理过程至关重要，而且对于以可控和可编程的方式操纵细胞行为也至关重要。
