The transduction of force into a biological signal is critical to all living organisms. Recently, disruption of ordered lipids has emerged as an 'atypical' force sensor in biological membranes; however, disruption has yet to link with canonical channel mechanosensation. Here we show that forceinduced disruption and lipid mixing activates TWIKrelated K + channel (TREK-1), and that this activation is dependent on phospholipase D2 (PLD2). PLD2 transduces the force into a chemical signal phosphatidic acid (PA) that is then sensed by TREK-1 with a latency of <3 ms. TREK-1 then produces a mechanically induced change in membrane potential. Hence, in a biological membrane, we show the ordered lipid is the force sensor, PLD2 is a chemical transducer, and the 'mechanosensitive' ion channel TREK-1 is a downstream effector of mechanical transduction. Confirming this central role for PA singling in force transduction, genetic deletion of PLD decreases mechanosensitivity and pain thresholds in D. melanogaster.

Purpose The SF-36 is a commonly used tool for measuring health status in a general population. Despite the overall moderate to high validity scores, we believe that certain communicative dynamics of the questionnaire deserve more careful attention. Our aim was to examine how pragmatic dynamics and epistemic reflection may influence answers to the SF-36.Methods We applied a three-step Gricean analysis, which included identification of the items in which pragmatic dynamics are most likely to have a significant effect, examination of how Gricean maxims might affect the answers given to the items identified, and finally, assessment of whether the combined influence of linguistic context-sensitivity and pragmatic norms is benign.Results Items 6, 9a, 10 and 11a–d were included in the analysis. Regarding these items, our analysis showed that the pragmatic dynamics of scalar implicatures are crucial to the interpretation of answer options. In addition, we raised concerns specifically about the answer option ‘Ved ikke’; rather than representing a neutral midpoint, the answer is compatible with both a positive and a negative answer option. Nonetheless, we found that the communicative dynamics of the questionnaire are mostly benign.Conclusion Compared to the significance of scalar implicatures, the potential effects of epistemic reflection that we identified are minor because they concern only items with a ‘Don’t know’ answer option. However, we raised the concern that attention to epistemic error possibilities might prompt respondents to opt for a ‘Don’t know’ answer despite having evidence supporting a different answer. Therefore, although pragmatic norms of communication are far more significant than attention to epistemic error possibilities in shaping answers to the SF-36, we think that both factors belong in a description of how the questionnaire works.