Abstract

Significance Mechanical force opens mechanosensitive ion channels in the cellular membrane to produce electrical signals that underlie sensation of touch, hearing, and other mechanical stimuli. An unanswered question is: How are mechanical forces transmitted to eukaryotic mechanosensitive channels in the membrane? We show that two mechanosensitive ion channels in eukaryotes, TRAAK (K2P4.1) and TREK1 (K2P2.1), are directly opened by mechanical force through the lipid membrane in the absence of all other cellular components. This finding extends the “force-from-lipid” paradigm established in bacterial channels to TRAAK and TREK1, eukaryotic mechanosensors.