(Invited) Stretchable Electrochemical Sensor for Inducing and Monitoring Cell Mechanotransduction in Real-Time

Nearly all kinds of cells within organisms are sensitive to mechanical forces and convert them into specific biochemical responses. This important and sophisticated process is described as mechanotransduction1. Several approaches are classically used to report on the ensuing modifications (gene expression, protein activity, etc.) expressed by cells in response to mechanical stimulations. Nonetheless, acquiring such evidences requires at least tens of minutes preventing any real-time information about the primary biochemical signals underlying mechanotransduction. Monitoring such presumably transient and weak signaling events since very early stages of cell mechanotransduction remains therefore an important challenge. Electrochemical sensing for detecting and quantifying transient release of biochemical molecules by living cells or tissues is widely accepted nowadays. In this regard, flexible and stretchable biocompatible electrochemical sensors should offer ideal platforms for applying mechanical strains and monitoring at the same time electroactive biochemical responses from mechanosensitive cells directly cultured on the sensor. However, up to date, despite several stimulating progresses in stretchable physical sensors and very few emerging successes in wearable electrochemical devices, no breakthrough concept has emerged for inducing cell mechanotransduction and investigating it in real-time by a single electrochemical device. Recently, we reported a high-performance stretchable electrode based on networks of gold nanotubes (Au NTs) deposited on polydimethylsiloxane (PDMS) thin films. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allowed for the first time, real-time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching-free and stretching states as well as sensing of the inner lining of blood vessels.2 However, the sensitivity and stability of the Au NTs/PDMS electrode were not sufficient to detect very weak transient signals triggered from cells by stretching strains only. This limitation was further overcomed by implementing a percolating CNTs network onto the Au NTs backbones through transfer of a free-standing CNTs ultrathin-film onto the Au NTs/PDMS electrode. This hybrid nano-structure provides the sensor with greatly enhanced mechanical and electrochemical performances while granting very good cellular compatibility, which allowed monitoring stretch-induced transient release of vasoactive molecules by endothelial cells cultured on this sensor and submitted to stretching strains. The work represents the first step toward real-time monitoring of cell mechanotransduction by electrochemical techniques, providing a promising way toward many other direct, in real time and in situ measurements of cell mechanotransduction. References: 1. N. Wang, J. D. Tytell, D. E. Ingber, Nat. Rev. Mol. Cell Biol. 2009, 10, 75-82. 2. Y. L. Liu, Z. H. Jin, Y. H. Liu, X. B. Hu, Y. Qin, J. Q. Xu, C. F. Fan, W. H. Huang, Angew. Chem. Int. Edit. 2016, 55, 4537-4541.