Abstract

ABSTRACTMechanosensation is crucial for cells to sense and respond to mechanical signals within their local environment. While adaptation allows a sensor to be conditioned by stimuli within the environment and enables its operation in a wide range of stimuli intensities, the mechanisms behind adaptation remain controversial in even the most extensively studied mechanosensor, bacterial mechanosensitive channels. Primary cilia are ubiquitous sensory organelles. They have emerged as mechanosensors across diverse tissues, including kidney, liver and the embryonic node, and deflect with mechanical stimuli. Here, we show that both mechanical and chemical stimuli can alter cilium stiffness. We found that exposure to flow stiffens the cilium, which deflects less in response to subsequent exposures to flow. We also found that through a process involving acetylation, the cell can biochemically regulate cilium stiffness. Finally, we show that this altered stiffness directly affects the responsiveness of the cell to mechanical signals. These results demonstrate a potential mechanism through which the cell can regulate its mechanosensing apparatus.

Highlights

  • Cellular sensing of physical cues is essential to homeostasis and its dysfunction leads to devastating diseases, including atherosclerosis, osteoporosis, and cancer (Hoffman et al, 2011)

  • We recently observed that cilia deflected by fluid flow often did not recover to their original positions after flow had ceased (Downs et al, 2014), suggesting flow can induce ciliary structural reorganization

  • Cilium’s sensory adaptation and the cilium may alter its mechanical properties in response to stimuli

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Summary

Introduction

Cellular sensing of physical cues is essential to homeostasis and its dysfunction leads to devastating diseases, including atherosclerosis, osteoporosis, and cancer (Hoffman et al, 2011). We show that the primary cilium is an adaptive mechanosensor and reveal a specific mechanism that can regulate cellular mechanosensitivity. These studies suggest length is one mechanism by which the cilium may adapt and regulate mechanosensitivity. Cilium’s sensory adaptation and the cilium may alter its mechanical properties in response to stimuli.

Results
Conclusion

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