Kavli Affiliate: Yuh Nung and Jan Yifan Cheng and Yuh Nung Jan
| Authors: Yukun Wang, Peng Jin, Avinash Kumar, Lily Jan, Yifan Cheng, Yuh-Nung Jan and Yongli Zhang
| Summary:
TCytoskeleton-tethered mechanosensitive channels (MSCs) utilize compliant proteins or protein domains called gating springs to convert mechanical stimuli into electric signals, enabling sound and touch sensation and proprioception. The mechanical properties of these gating springs, however, remain elusive. Here, we explored the mechanical properties of the homotetrameric NompC complex containing long ankyrin-repeat domains (ARDs). We developed a toehold-mediated strand displacement approach to tether single membrane proteins, allowing us to exert force on them and precisely measure their absolute extension using optical tweezers. Our findings revealed that each ARD has a low stiffness of ∼0.7 pN/nm and begins to unfold stepwise at ∼7 pN, leading to nonlinear compliance. Our calculations indicate that this nonlinear compliance may help regulate NompC’s sensitivity, dynamic range, and kinetics to detect mechanical stimuli. Overall, our research highlights the importance of a compliant and unfolding-refolding gating spring in facilitating a graded response of MSC ion transduction across a wide spectrum of mechanical stimuli.