Tabrizi, M. A. | bioRxiv Science

bioRxiv2024

A portable electrochemical DNA sensor for sensitive and tunable detection of piconewton-scale cellular forces

Cell-generated forces are a key player in cell biology, especially during cellular shape formation, migration, cancer development, and immune response. A new type of label-free smartphone-based electrochemical DNA sensor is developed here for cellular force measurement. When cells apply tension forces to the DNA sensors, the rapid rupture of DNA duplexes allows multiple redox reporters to reach the electrode and generate highly sensitive electrochemical signals. The sensitivity of these portable sensors can be further enhanced by incorporating a CRISPR-Cas12a system. Meanwhile, the threshold force values of these DNA-based sensors can be rationally tuned based on the force application geometries and also DNA intercalating agents. Overall, these highly sensitive, portable, cost-efficient, and easy-to-use electrochemical sensors can be powerful tools for detecting different cell-generated molecular forces. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/586508v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@e9bb33org.highwire.dtl.DTLVardef@10114d0org.highwire.dtl.DTLVardef@1fd925dorg.highwire.dtl.DTLVardef@942a20_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2023

Electrochemical DNA-based sensors for measuring cell-generated forces

Mechanical forces play an important role in cellular communication and signaling. We developed in this study novel electrochemical DNA-based force sensors for measuring cell-generated adhesion forces. Two types of DNA probes, i.e., tension gauge tether and DNA hairpin, were constructed on the surface of a smartphone-based electrochemical device to detect piconewton-scale cellular forces at tunable levels. Upon experiencing cellular tension, the unfolding of DNA probes induces the separation of redox reporters from the surface of the electrode, which results in detectable electrochemical signals. Using integrin-mediated cell adhesion as an example, our results indicated that these electrochemical sensors can be used for highly sensitive, robust, simple, and portable measurement of cell-generated forces.

biophysics↗