A closed-loop system for millisecond readout and control of membrane tension.
Michael J Sindoni and Jörg Grandl. Biophysical Journal. 2025.
We build a closed-loop system for millisecond readout and control of membrane tension, which effectively functions as a tension clamp.
Piezo1 ion channels are capable of conformational signaling.
Amanda H Lewis, Marie E Cronin, and Jörg Grandl. Neuron. 2024.
Here we report that Piezo1 ion channels can signal to other proteins solely by changing their shape (conformation), independently of ion permeation through them.
Subconductance states add complexity to Piezo1 gating model.
Marie E Cronin and Jörg Grandl. Trends in Biochemical Sciences. 2024.
Our Spotlight article highlights recent work from Allah, Nosyreva, and colleagues that characterizes Piezo1 partial channel openings, known as subconductance states, and develops a new gating model of Piezo1 function.
Piezo Ion Channels.
Jörg Grandl and Bailong Xiao. Handbook of Ion Channels, 2nd edition.
This book chapter discusses the established concepts of Piezo structure, function, and physiology and outlines areas that are subject of ongoing investigations.
The energetics of rapid cellular mechanotransduction.
Michael N Young, Michael J Sindoni, Amanda H Lewis, Stefan Zauscher, and Jörg Grandl. PNAS. 2023.
We find that, depending on the ion channel expressed, cells can function either as proportional or nonlinear transducers of mechanical energy and detect mechanical energies as little as ~100 fJ, with a resolution of up to ~1 fJ.
Physics of mechanotransduction by Piezo ion channels.
Michael N Young, Amanda H Lewis, and Jörg Grandl. J Gen Physiol. 2022.
We compare the three predominant mechanisms likely to explain Piezo activation-the force-from-lipids mechanism, the tether model, and the membrane footprint theory.
Piezo1 ion channels inherently function as independent mechanotransducers.
Amanda H Lewis and Jörg Grandl. Elife. 2021.
Our data, together with stochastic simulations of Piezo1 spatial distributions, show that both at endogenous densities (1-2 channels/μm2), and at non-physiological densities (10-100 channels/μm2) predicted to cause substantial footprint overlap, Piezo1 density has no effect on its pressure sensitivity or open probability in the nominal absence of membrane tension.
Stretch and poke stimulation for characterizing mechanically activated ion channels.
Amanda H Lewis and Jörg Grandl. Methods Enzymol. 2021.
Here, we review the general methods of stretch and poke stimulation and discuss the advantages and disadvantages of each.
An Internal Dial for Sensitivity and Gain of Rapid Mechanotransduction.
Amanda H Lewis and Jörg Grandl. Neuron. 2020.
We comment on the discovery of a novel Piezo1 variant with distinct functional properties, providing key insights into Piezo’s structure and function that were fully unexpected.
Inactivation Kinetics and Mechanical Gating of Piezo1 Ion Channels Depend on Subdomains within the Cap.
Amanda H Lewis and Jörg Grandl. Cell Reports. 2020.
We identify three small subdomains within the extracellular cap that individually can confer the distinct kinetics of inactivation of Piezo2 onto Piezo1.
A cellular mechanism for age-induced itch.
Amanda H Lewis and Jörg Grandl. Science. 2018.
We comment on a paper reporting how age-induced loss of touch signaling causes mechanical itch.
Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C-Terminal Extracellular Domain and the Inner Pore Helix.
Jason Wu, Michael N Young, Amanda H Lewis, Ashley N Martfeld, Breanna Kalmeta, and Jörg Grandl. Cell Reports. 2017.
We identify the globular C-terminal extracellular domain of Pierzos as a structure that is sufficient to confer the time course of inactivation and a single positively charged lysine residue at the adjacent inner pore helix as being required for its voltage dependence.
Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels.
Amanda H Lewis, Alisa F Cui, Malcolm F McDonald, and Jörg Grandl. Cell Reports. 2017.
We find that Piezo channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration.
TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity.
Jason O Sosa-Pagán, Edwin S Iversen, and Jörg Grandl. Scientific Reports. 2017.
We found that strong decreases in hydrophobicity of amino acids of TRPV! are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation.
Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels.
Jason Wu, Amanda H Lewis, and Jörg Grandl. Trends in Biochemical Sciences. 2017.
Here, we review how groundbreaking research that has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel.
Localized force application reveals mechanically sensitive domains of Piezo1.
Jason Wu, Raman Goyal, and Jörg Grandl. Nature Communications. 2016.
We use magnetic nanoparticles as localized transducers of mechanical force in combination with pressure-clamp electrophysiology to identify mechanically sensitive domains of Piezo1 important for activation and inactivation.
Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension.
Amanda H Lewis and Jörg Grandl. Elife. 2015.
We find that Piezo1 responds to lateral membrane tension with exquisite sensitivity as compared to other mechanically activated channels and that resting tension can drive channel inactivation, thereby tuning overall mechanical sensitivity of Piezo1.
The pore-domain of TRPA1 mediates the inhibitory effect of the antagonist 6-methyl-5-(2-(trifluoromethyl)phenyl)-1H-indazole.
Hans Moldenhauer, Ramon Latorre, and Jörg Grandl. PLoS One. 2014.
We found that the single-point mutation I624N in the N-terminus of TRPA1 specifically affects the sensitivity to mustard-oil, but not to cold temperatures.
Directionality of temperature activation in mouse TRPA1 ion channel can be inverted by single-point mutations in ankyrin repeat six.
Sairam Jabba, Raman Goyal, Jason O Sosa-Pagán, Hans Moldenhauer, Jason Wu, Breanna Kalmeta, Michael Bandell, Ramon Latorre, Ardem Patapoutian, and Jörg Grandl. Neuron. 2014.
We identified three single-point mutations that are individually sufficient to make mouse TRPA1 warm activated, while leaving sensitivity to chemicals unaffected.
