Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain.

Background: Voltage-gated potassium channels are regulated by their lipid environment. Results: The first lipids KvAP channels come in contact with can only be exchanged if the channel is in the open state. Conclusion: Lipids bound to K v channels are accessible only in a state-dependent manner. Significance: The high affinity between lipids and integral membrane protein suggests that both should be treated as one complex.

Background: For Kv channels, only crystal structures for the open state are available. Results: Using LRET, we determined the movement of the S4-S5 linker during gating in KvAP channels. Conclusion: A small displacement of the S6 by only 4 Å is sufficient for closing of the Kv channels. Significance: We provide the first Kv channel closed state model based on cytosolic restraints.

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measuring both force and torque, has been developed as a versatile setup in tackling biologically relevant issues at high spatial and temporal resolution. Torque control in this optical tweezers setup relies on the manipulation and readout of the polarization state of light used to trap nano-fabricated birefringent cylinders. The flagellar motor of Escherichia coli is a well-know rotary motor of only about 45 nm embedded in the cellular membrane, but besides its protein content the exact functioning of this intriguing motor remains unknown. The rotary motor consists of a rotor attached to a flagellum and of stators 'pushing' the rotor around. Stators diffuse in the cytoplasmic membrane upon engaging in the motor complex. The temporal resolution of our setup allows to investigate fast stator dynamics. We are studying the response of the motor at stall torque, forward rotation and backward rotation by optically adjusting the load torque on the motor, on which we present preliminary results. Deploying our optical setup we are trying to unravel the mechanism by which this molecular motor works to propel bacteria.