Mechano-Cas12a Assisted Tension Sensor (MCATS) for Massively Amplified Cell Traction Force Measurements

Duan, Y.; Szlam, F.; Hu, Y.; Chen, W.; Li, R.; Ke, Y.; Sniecinski, R.; Salaita, K.

doi:10.1101/2022.10.26.513907

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bioRxiv · 10.1101/2022.10.26.513907

Mechano-Cas12a Assisted Tension Sensor (MCATS) for Massively Amplified Cell Traction Force Measurements

Duan, Y.·Szlam, F.·Hu, Y.·Chen, W.·Li, R.·Ke, Y.·Sniecinski, R.·Salaita, K.

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Abstract

Cells transmit piconewton forces to mediate essential biological processes such as coagulation. One challenge is that cell-generated forces are infrequent, transient, and difficult to detect. Here, we report the development of Mechano-Cas12a Assisted Tension Sensor (MCATS) that utilizes CRISPR-Cas12a to transduce and amplify the molecular forces generated by cells. We demonstrate the power of MCATS by detecting the forces generated by as few as ~103 human platelets in a high-throughput manner. Platelet forces are significantly inhibited when blood samples are treated with FDA-approved drugs such as aspirin, eptifibatide(integrilin(R)), 7E3(Reopro(R)), and ticagrelor (Brelinta(R)). Because MCATS requires <5uL of blood/measurement, a single blood draw can generate a personalized dose-response curve and IC50 for this panel of drugs. Platelet activity and force-generation are tightly associated, and hence MCATS was used to quantify platelet dysfunction following cardiopulmonary bypass (CPB) in a pilot study of 7 cardiac patients. We found that MCATS detected platelet dysfunction which strongly correlated with the need for platelet transfusion to limit bleeding. These results indicate MCATS may be a useful assay for clinical applications.

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Duan, Y., Szlam, F., Hu, Y., Chen, W., Li, R., Ke, Y., Sniecinski, R., Salaita, K.. 2022-10-27. Mechano-Cas12a Assisted Tension Sensor (MCATS) for Massively Amplified Cell Traction Force Measurements. https://doi.org/10.1101/2022.10.26.513907

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