Scholars@Duke
Jorg Grandl

Jorg Grandl

Associate Professor of Neurobiology
Neurobiology
grandl@neuro.duke.edu
Box 3209 Med Ctr, Durham, NC 27710
Bryan Research Building, 311 Research Drive Room 327G, Durham, NC 27710

Selected Publications

A closed-loop system for millisecond readout and control of membrane tension.

Journal Article Biophys J · March 30, 2025 Characterizing the function of force-gated ion channels is essential for understanding their molecular mechanisms and how they are affected by disease-causing mutations, lipids, or small molecules. Pressure-clamp electrophysiology is a method that is estab ... Full text Link to item Cite

Piezo1 ion channels are capable of conformational signaling.

Journal Article Neuron · September 25, 2024 Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P) ... Full text Link to item Cite

Subconductance states add complexity to Piezo1 gating model.

Journal Article Trends Biochem Sci · July 2024 Piezos are force-gated ion channels that detect and communicate membrane tension to the cell. Recent work from Ullah, Nosyreva, and colleagues characterizes partial channel openings, known as subconductance states, and develops a new gating model of Piezo1 ... Full text Link to item Cite

Piezo1 ion channels are capable of conformational signaling.

Journal Article bioRxiv · May 29, 2024 Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P) ... Full text Open Access Link to item Cite

The energetics of rapid cellular mechanotransduction.

Journal Article Proc Natl Acad Sci U S A · February 21, 2023 Cells throughout the human body detect mechanical forces. While it is known that the rapid (millisecond) detection of mechanical forces is mediated by force-gated ion channels, a detailed quantitative understanding of cells as sensors of mechanical energy ... Full text Link to item Cite

The energetics of rapid cellular mechanotransduction

Conference BIOPHYSICAL JOURNAL · 2023 Cite

Piezo Channels

Chapter · January 1, 2023 Piezo1 and Piezo2 are mechanically activated nonselective cation channels. Piezos are found in protists, plants and all metazoans where they function as sensors of mechanical forces. Several human diseases have been genetically linked to Piezos, but the un ... Full text Cite

Physics of mechanotransduction by Piezo ion channels.

Journal Article J Gen Physiol · July 4, 2022 Piezo ion channels are sensors of mechanical forces and mediate a wide range of physiological mechanotransduction processes. More than a decade of intense research has elucidated much of the structural and mechanistic principles underlying Piezo gating and ... Full text Link to item Cite

Piezo1 ion channels inherently function as independent mechanotransducers.

Journal Article Elife · October 29, 2021 Featured Publication Piezo1 is a mechanically activated ion channel involved in sensing forces in various cell types and tissues. Cryo-electron microscopy has revealed that the Piezo1 structure is bowl-shaped and capable of inducing membrane curvature via its extended footprin ... Full text Open Access Link to item Cite

Stretch and poke stimulation for characterizing mechanically activated ion channels.

Chapter · 2021 Quantitative functional characterization of mechanically activated ion channels is most commonly achieved by a combination of patch-clamp electrophysiology and stimulation by stretch (or pressure-clamp) and poke (or cell-indentation). A variety of stretch ... Full text Link to item Cite

An Internal Dial for Sensitivity and Gain of Rapid Mechanotransduction.

Journal Article Neuron · May 6, 2020 Piezos are ion channels that are activated by mechanical force. Now, 10 years after their initial discovery, Geng et al. (2020) reports, in this issue of Neuron, a novel Piezo1 variant with distinct functional properties, providing key insights into Piezo' ... Full text Link to item Cite

Inactivation Kinetics and Mechanical Gating of Piezo1 Ion Channels Depend on Subdomains within the Cap.

Journal Article Cell Rep · January 21, 2020 Piezo1 ion channels are activated by mechanical stimuli and mediate the sensing of blood flow. Although cryo-electron microscopy (cryo-EM) structures have revealed the overall architecture of Piezo1, the precise domains involved in activation and subsequen ... Full text Link to item Cite

Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes.

Journal Article Cell Rep · January 29, 2019 Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained ... Full text Link to item Cite

Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C-Terminal Extracellular Domain and the Inner Pore Helix.

Journal Article Cell Rep · November 28, 2017 Featured Publication Piezo proteins form mechanically activated ion channels that are responsible for our sense of light touch, proprioception, and vascular blood flow. Upon activation by mechanical stimuli, Piezo channels rapidly inactivate in a voltage-dependent manner throu ... Full text Link to item Cite

Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects.

Journal Article Sci Signal · October 10, 2017 Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are pre ... Full text Open Access Link to item Cite

Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels.

Journal Article Cell Rep · June 20, 2017 Featured Publication Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping acros ... Full text Link to item Cite

Endogenous Piezo1 Can Confound Mechanically Activated Channel Identification and Characterization.

Journal Article Neuron · April 19, 2017 Featured Publication A gold standard for characterizing mechanically activated (MA) currents is via heterologous expression of candidate channels in naive cells. Two recent studies described MA channels using this paradigm. TMEM150c was proposed to be a component of an MA chan ... Full text Link to item Cite

TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity.

Journal Article Sci Rep · April 3, 2017 Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. ... Full text Link to item Cite

Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels.

Journal Article Trends Biochem Sci · January 2017 Featured Publication In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction ... Full text Link to item Cite

Localized force application reveals mechanically sensitive domains of Piezo1.

Journal Article Nat Commun · October 3, 2016 Featured Publication Piezos are mechanically activated ion channels that function as sensors of touch and pressure in various cell types. However, the precise mechanism and structures mediating mechanical activation and subsequent inactivation have not yet been identified. Her ... Full text Link to item Cite

Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension.

Journal Article Elife · December 8, 2015 Featured Publication Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent mechanical sensitivity of Piezo1 varies substantially across cellular environments, stimulating ... Full text Link to item Cite

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.

Journal Article Proc Natl Acad Sci U S A · November 25, 2014 Featured Publication Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical l ... Full text Open Access Link to item Cite

The pore-domain of TRPA1 mediates the inhibitory effect of the antagonist 6-methyl-5-(2-(trifluoromethyl)phenyl)-1H-indazole.

Journal Article PLoS One · 2014 The transient receptor potential ion channel TRPA1 confers the ability to detect tissue damaging chemicals to sensory neurons and as a result mediates chemical nociception in vivo. Mouse TRPA1 is activated by electrophilic compounds such as mustard-oil and ... Full text Link to item Cite

Single residues in the outer pore of TRPV1 and TRPV3 have temperature-dependent conformations.

Journal Article PLoS One · 2013 Featured Publication Thermosensation is mediated by ion channels that are highly temperature-sensitive. Several members of the family of transient receptor potential (TRP) ion channels are activated by cold or hot temperatures and have been shown to function as temperature sen ... Full text Link to item Cite

Piezo proteins are pore-forming subunits of mechanically activated channels.

Journal Article Nature · February 19, 2012 Featured Publication Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, res ... Full text Link to item Cite

High-Throughput Approaches to Studying Mechanisms of TRP Channel Activation

Chapter · 2011 Transient receptor potential (TRP) channels are calcium-permeable nonselective cation channels with six transmembrane (TM) domains and a putative pore loop between TM5 and TM6. About 28 mammalian TRP channels have been identified so far, with different num ... Cite

Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain.

Journal Article Nat Neurosci · June 2010 Featured Publication TRPV1 is the founding and best-studied member of the family of temperature-activated transient receptor potential ion channels (thermoTRPs). Voltage, chemicals and heat allosterically gate TRPV1. Molecular determinants of TRPV1 activation by capsaicin, all ... Full text Link to item Cite

Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4.

Journal Article Proc Natl Acad Sci U S A · February 3, 2009 Temperature-activated transient receptor potential ion channels (thermoTRPs) are polymodal detectors of various stimuli including temperature, voltage, and chemicals. To date, it is not known how TRP channels integrate the action of such disparate stimuli. ... Full text Link to item Cite

Pore region of TRPV3 ion channel is specifically required for heat activation.

Journal Article Nat Neurosci · September 2008 Featured Publication Ion channels can be activated (gated) by a variety of stimuli, including chemicals, voltage, mechanical force or temperature. Although molecular mechanisms of ion channel gating by chemical and voltage stimuli are understood in principal, the mechanisms of ... Full text Link to item Cite

Functional asymmetry of transmembrane segments in nicotinic acetylcholine receptors.

Journal Article Eur Biophys J · October 2006 Nicotinic acetylcholine receptors are heteropentameric ion channels that open upon activation to a single conducting state. The second transmembrane segments of each subunit were identified as channel-forming elements, but their respective contribution in ... Full text Link to item Cite

Engineered site-directed labeling of nicotinic acetylcholine receptors using reactive epibatidine derivatives: appraisal of epibatidine-docking models in neuronal and muscular receptors.

Conference J Mol Neurosci · 2006 We developed an engineered site-directed labeling method (Foucaud et al., 2001) to investigate ligand receptor interactions on the acetylcholine (ACh)- binding site of nicotinic acetylcholine receptors (nAChRs). The method uses cysteine receptor mutants, t ... Full text Link to item Cite