hERG | KV11.1 | Erg Related Potassium Channel Member 2
Family:
Potassium channels
Subgroups:
Shaker (KV1.1–KV1.8), Shab (KV2.1-KV2.2), Shaw (KV3.1–KV3.4), Shal (KV4.1–KV4.3), KQT like (KV7.1–KV7.5), Eag related (KV10.1-KV10.2), Erg related (KV11.1–KV11.3), Elk related (KV12.1)
Topology:
Contains six transmembrane domains (S1–S6), four single subunits form a pore, homotetramers and heterotetramers are possible.
hERG (KV11.1) Background Information
KV11.1, better known as hERG (human Ether-à-go-go-Related Gene), contributes to the electrical activity of the heart that coordinates the heart's beating (i.e., the hERG channel mediates the repolarizing IKR current in the cardiac action potential). When this channel's ability to conduct electrical current across the cell membrane is inhibited or compromised, either by application of drugs or by rare mutations in some families, it can result in a potentially fatal disorder called long QT syndrome; a number of clinically successful drugs in the market have had the tendency to inhibit hERG, and create a concomitant risk of sudden death, as a side-effect, which has made hERG inhibition an important antitarget that must be avoided during drug development. Due to the documented potential of QT interval prolonging drugs, the United States Food and Drug Administration issued recommendations for the establishment of a cardiac safety profile during pre-clinical drug development: ICH S7B.
hERG has also been associated with modulating the functions of some cells of the nervous system and with establishing and maintaining cancer-like features in leukemic cells.
Gene:
KCNH2
Human Protein:
UniProt Q12809
Tissue:
brain, heart
Function/ Application:
Cardiac IKR current, cell proliferation, cell migration
Pathology:
Long QT syndrome (LQT2), SQT1, atrial fibrillation, sudden infant death syndrome, cancer
Interaction:
KCNH6/ERG2, KCNH7/ERG3, ALG10B, KCNE1, KCNE2, CANX, cAMP, caveolin-1, FHL2
Modulator:
Terfenadine, verapamil, dofetilide, cisapride, astemizole, E4031
Assays:
Patch Clamp: whole cell, room temperature, physiological temperature
Recommended Reviews:
Gutman et al. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev 57(4):473-508
Data and Applications
hERG - Pharmacology at Physiological Temperature using the CiPA Protocol
SyncroPatch 384/768 PE (a predecessor model of the SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.
Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol at 35 degree Celsius. Measured on the SyncroPatch 384PE using perforated patch clamp methodology (Escin) and multi-hole chips (4 holes per well). The IC50 value of Erythromycin of the peak current was determined as 60.5 µM.
hERG - Pharmacology of Cisapride, using the CiPA protocol
Patchliner data and applications:
Cells were kindly provided by Charles River.
The effect of cisapride on hERG currents was investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Cisapride was determined as 112 nM.
hERG - Pharmacology using the CiPA Protocol
SyncroPatch 384/768 PE (a predecessor model of SyncroPatch 384/768i) data and applications:
Cells were kindly provided by Charles River.
Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using whole cell patch clamp methodology and multi-hole chips (4 holes per well). The IC50 value of the following compounds of the peak current was determined as 4.18 µM for Diltiazem, 37.4 nM for Terfenadine, 971 nM for Quinidine, 63 µM for Mexiletine, 431 nM for Verapamil and 4.54 µM for Ranolazine.
hERG - recordings with great stability using the CiPA step ramp protocol
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River.
Screenshots of the PatchControl 384 software showing hERG current traces in response to the CiPA voltage step protocol. Measured on the SyncroPatch 384PE using perforated patch clamp methodology (Escin) and multi-hole chips (4 holes per well).
Cardiac Ion Channels - Pharmacology of Vandetanib
CardioExcyte 96 and Patchliner data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.
The image on the left hand side displays the results of the blocking effect of Vandetanib on hERG, NaV1.5, CaV1.2 and KV4.3. The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 1 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility.
Cardiac Ion Channels - Pharmacology of Sotalol
CardioExcyte 96 and SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.
The image on the left hand side displays the results of the blocking effect of Sotalol on hERG. The result is in good agreement with manual patch clamp data (Crumb et al., 2016). The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 10 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility measurements.
hERG - Application of "Sticky Compounds"
Patchliner data and applications:
hERG expressing HEK293 cells were kindly provided by Cytomyx/Millipore.
Even sticky compounds pose no problem for the Patchliner. IC50 measurements of well known sticky substances were determined on the Patchliner: Terfenadine IC50 = 11.0 ± 3 nM, Flunarizine IC50 163.7 ± 19 nM and Cisapride IC50 8.9 ± 3 nM.
hERG - Efficient Screening
Patchliner data and applications:
Cells were kindly provided by Cytomyx/Millipore.
The effects of six different blockers (terfenadine, cisapride, E4031, astemizole, propafenone, quinidine) on hERG currents (HEK293 cells) were investigated. Expected IC50 values for the different compounds were obtained. In two days, 119 full dose response curves were collected by a single person. Data was analyzed using Nanion’s Data Analysis Package, a very efficient and convenient data analysis tool!
hERG - Pharmacological Experiments at 35 °C
Port-a-Patch data and applications:
Cells were kindly provided by Cytomyx/Millipore, UK.
A full dose response curve of quinidine acting on the hERG channel was obtained at physiological temperature (35 °C). The IC50 for quinidine at physiological temperature was 1.3 ± 0.2 μM (n = 5), similar to that obtained at room temperature (1.0 ± 0.03 μM, n = 3).
hERG - Good Results with "Sticky Compounds"
Port-a-Patch data and applications:
Cells were kindly provided by Cytomyx/Millipore.
Sticky compounds, such as some hERG blockers, exhibit expected IC50 values with the Port-a-Patch. The concentrations of the half maximal block were: 1.27 nM (astemizole), 8.9 nM (cisapride), 163.7 nM (flunarizine) and 11.0 nM (terfenadine).
hERG - Simple Data Analysis
Patchliner data and applications:
With our analysis tools, especially programmed routines in Igor make dose response curves, raw data and current time courses easily accessible. Also, creating average dose response curves over multiple experiments - even conducted on different days - remains easy.
hERG - Block at Physiological Temperature
Patchliner data and applications:
Cells were kindly provided by Cytomyx/Millipore, UK.
The effects of erythromycin on hERG currents were tested at different temperatures. Erythromycin has been shown to block hERG channels at physiological temperature with an IC50 of approx. 40 µM. However, at RT erythromycin is much less potent. For more details on these experiments please refer to the Application Note.
hERG - Temperature Control
Port-a-Patch data and applications:
Cells were kindly provided by Cytomyx/Millipore.
The image shows example traces for hERG mediated currents at 25 ± 2 °C (black) and 35 ± 2 °C (blue). The peak current amplitude was increased at 35 °C, and the rise time and decay time constants were faster at physiological temperature compared with those obtained at room temperature.
hERG - Stable Recordings with Accurate Pharmacology
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) data and applications:
Cells were kindly provided by Charles River Laboratories.
Current-voltage relationship of hERG (Kv11.1) expressed in HEK293 is shown along with pharmacology of 4 hERG-active compounds. The current-voltage relationships for all 384 wells (top) using perforated patch (Escin) and multi-hole chips (4 holes per well) are shown. In all 384 wells, a hERG-mediated current was observed with peak amplitude >700 pA at -20 mV. Using a pharmacology voltage protocol, experiments were stable lasting over 20 minutes. Concentration response curves for astemizole, pimozide, cisapride and terfenadine revealed IC50 values consistent with those found in the literature.
hERG - Current Voltage Relationship
SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Cytomyx Millipore.
Borosilicate glass chips are used as the patch clamp substrate, ensuring excellent voltage control of the cell membrane and high quality seals. Voltage gated channels such as hERG (expressed in HEK293) have been used to validate the system. These traces show the raw current responses of a single cell to a hERG IV pulse protocol. The data were recorded on the SyncroPatch 96. In the upper screenshot raw current traces are shown. In the lower one the same current traces after leak subtraction are shown.
hERG - Stable Recordings
Patchliner data and applications:
Cells were kindly provided by Cytomyx/Millipore, UK.
A series of drug concentrations can be applied to each cell. The top figures show the original traces and the corresponding average dose-response curve. Five concentrations of Quinidine (0.1, 0.3, 1, 3 and 10 μM) have been applied.
The lower figure shows the corresponding Imax (-40 mV) including a wash out step and an additional application of the blocker to demonstrate the stability of whole cell recordings.
Cardiomyocytes - Time-dependent effect of Pentamidine on Cor.4U cardiomyocytes
CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.
Time-dependent effect of Pentamidine on Cor.4U cardiomyocytes. Pentamidine clinically causes acquired long QT syndrome, which is associated with prolonged QT intervals, tachycardias, and sudden cardiac arrest. Pentamidine delays terminal repolarization in human heart by acutely blocking cardiac inward rectifier currents. At the same time, it reduces surface expression of the cardiac potassium channel IKr/human ether à-go-go-related gene (hERG).
Insets: EFP raw traces and online analysis value FPDc in the presence of Pentamidine (10 µM) at different timepoints.
hERG - Pharmacology of Bepridil, Dofetilide, Cisapride, Diltiazem (Results CiPA Phase I Study)
Patchliner data and applications:
Cells were kindly provided by Charles River.
The effect of four compounds on hERG currents were investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Cisapride was determined as 112 nM, Bepridil as 178 nM, Dofetilide as 33.9 nM and Diltiazem as 14.5 µM.
hERG - Pharmacology of Mexiletine, Quinidine, Ondansetron, Ranolazine (Results CiPA Phase I Study)
Patchliner data and applications:
Cells were kindly provided by Charles River.
The effect of four compounds on hERG currents were investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Mexiletine was determined as 77.3 µM, Quinidine as 1.04 µM, Ondansetron as 1.13 µM and Ranolazine as 11.9 µM.
hERG - Pharmacology of Sotalol, Terfenadine, Verapamil (Results CiPA Phase I Study)
Patchliner data and applications:
Cells were kindly provided by Charles River.
The effect of four compounds on hERG currents were investigated, using the CiPA voltage step protocol. Measured on the Patchliner the perforated patch methodology (Escin) and multi-hole chips (4 holes per well) were used. The IC50 value of Sotalol was determined as 157 µM, Terfenadine as 82.8 nM and Verapamil as 485 nM.
Application Notes
Cardiac Ion Channels - "High Throughput Screening of Cardiac Ion Channels"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) Patchliner CardioExcyte 96 application note 
(2.3 MB)
Cardiac Ion Channels - "Simultaneous Assessment of CiPA Stipulated Ion Channels on the SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (1.3 MB)
Cells were kindly provided by Charles River.
Cardiomyocytes - "Combining automated patch clamp, impedance and EFP of hiPSC-CMs"
CardioExcyte 96 SyncroPatch 3984PE (a predecessor model of SyncroPatch 384i) Patchliner Application Note
Cells kindly provided by Takara-Clonetech.
Cardiomyocytes - "Impedance and EFP recordings of Cor.4U cells using Nanion’s CardioExcyte 96"
CardioExcyte 96 Application Note (1.3 MB)
Cells were kindly provided by Ncardia.
Cardiomyocytes - "Impedance and EFP recordings of iCell Cardiomyocytes² on the CardioExcyte 96"
CardioExcyte 96 Application Note (2.8 MB)
Cells were kindly provided by Cellular Dynamics.
Cardiomyocytes - "Impedance and EFP recordings of Pluricyte Cardiomyocytes on the CardioExcyte 96"
CardioExcyte 96 Application Note (1.3 MB)
Cells were kindly provided by Ncardia.
Cardiomyocytes - "Voltage and current clamp recordings of Cor.4U human iPS cell-derived cardiomyocytes on Nanion’s Patchliner"
Patchliner application note: (0.6 MB)
Cells were kindly provided by Axiogenesis.
hERG - "Characterization of hERG (CHO) on Nanion's Port-a-Patch"
Port-a-Patch application note: (0.6 MB)
Cells were kindly provided by Millipore.
hERG - "Characterization of hERG (HEK293) on Nanion's Port-a-Patch"
Port-a-Patch application note: (0.7 MB)
Cells were kindly provided by Millipore.
hERG - "Effect of temperature on erythromycin action on hERG currents recorded on Nanion's Patchliner"
Patchliner application note: (0.9 MB)
Cells were kindly provided by Millipore.
hERG - "High Throughput Pharmacology of hERG Channels on Nanion’s SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) application note (0.6 MB)
hERG - "Pharmacology of hERG recorded on Nanion´s Port-a-Patch"
Port-a-Patch application note: (0.4 MB)
Cells were kindly provided by Millipore.
hERG - "Temperature controlled hERG recordings on the Port-a-Patch"
Port-a-Patch application note: (0.5 MB)
Cells were kindly provided by Millipore.
Publications
2019 - Rapid characterisation of hERG channel kinetics II: temperature dependence
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) pre-publication in BioRxiv (2019)
Authors:
Lei C.L., Clerx M., Beattie K.A., Melgari D., Hancox J.C., Gavaghan D.J., Polonchuk L., Wang K., Mirams G.R.
2019 - Rapid characterisation of hERG channel kinetics I: using an automated high-throughput system
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) pre-publication in BioRxiv (2019)
Authors:
Lei C.L., Clerx M., Beattie K.A., Gavaghan D.J., Polonchuk L., Mirams G.R., Wang K.
2019 - Postpartum hormones oxytocin and prolactin cause pro-arrhythmic prolongation of cardiac repolarization in long QT syndrome type 2
Port-a Patch Publication in EP Europace (2019)
Authors:
Bodi I., Sorge J., Castiglione A., Glatz S.M., Wuelfers E.M., Franke G., Perez-Feliz S., Koren G., Zehender M., Bugger H., Seemann G., Brunner M., Bode C., Odening K.E.
2019 - Electrophysiological evaluation of pentamidine and 17-AAG in human stem cell-derived cardiomyocytes for safety assessment
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) article in European Journal of Pharmacology (2019)
Authors:
Asahi Y., Nomura F., Abe Y., Doi M., Sakakura T., Takasuna K., Yasuda K.
2019 - Compounds commonly used in equine medicine inhibits the voltage-gated potassium channel Kv11.1
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Research in Veterinary Science (2019)
Authors:
Calloe K., Rognant, S., Friis S., Shaughnessy C., Klaerke D.A., Trachsel D.
2019 - Avoiding hERG-liability in drug design via synergetic combinations of different (Q)SAR methodologies and data sources: a case study in an industrial setting
Patchliner publication in Journal of Cheminformatics (2019)
Authors:
Hanser T., Steinmetz F.P., Plante J., Rippmann F., and Krier M.
2018 - Reconstitution and Electrophysiological Characterization of Ion Channels in Lipid Bilayers
Port-a-Patch and 
Vesicle Prep Pro publication in Current Protocols in Pharmacology (2018)
Authors:
Klaerke D.A., de los Angeles Tejada M., Grøsfjeld Christensen V., Lassen M., Amstrup Pedersen P., Calloe K.
2018 - Evaluation of possible proarrhythmic potency: comparison of the effect of dofetilide, cisapride, sotalol, terfenadine and verapamil on hERG and native IKr currents and on cardiac action potential
Patchliner publication in Toxicological Sciences (2018)
Authors:
Orvos P., Kohajda Z., Szlovák J., Gazdag P., Árpádffy-Lovas T., Tóth D., Geramipour A., Tálosi L., Jost N., Varró A., Virág L.
2018 - Dehydroevodiamine and hortiamine, alkaloids from the traditional Chinese herbal drug Evodia rutaecarpa, are IKr blockers with proarrhythmic effects in vitro and in vivo
Patchliner publication in Pharmacological Research (2018)
Authors:
Baburin I., Varkevisser R., Schramm A., Saxena P., Beyl S., Szkokan P., Linder T., Stary-Weinzinger A., van der Heyden M.A.G., Houtman M., Takanari H., Jonsson M., Beekman J.H.D., Hamburger M., Vos M.A., Hering S.
2018 - Cross-site comparison of excitation-contraction coupling using impedance and field potential recordings in hiPSC cardiomyocytes
CardioExcyte 96 publication in Journal of Pharmacological and Toxicological Methods (2018)
Authors:
Bot C.T., Juhasz K., Haeusermann F., Polonchuk L., Traebert M., Stölzle-Feix S.
2017 - Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer's disease
Patchliner publication in PLoS ONE (2017)
Authors:
Kim T., Yang H.Y., Park B.G., Jung S.Y., Park J.H., Park K.D., Min S.J., Tae J., Yang H., Cho S., Cho S.J., Song H., Mook-Jung I., Lee J., Pae A.N.
2017 - Correlation between human ether-a-go-go related gene channel inhibition and action potential prolongation
Patchliner publication in British Journal of Pharmacology (2017)
Authors:
Saxena P., Hortigon‐Vinagre M.P., Beyl S.,Baburin I., Andranovits S., Iqbal S.M., Costa A., IJzerman A.P., Kügler P., Timin E., Smith G.L., Hering S.
2017 - Combined Impedance and Extracellular Field Potential Recordings from Human Stem Cell-Derived Cardiomyocytes
CardioExcyte 96 book chapter in Stem Cell-Derived Models in Toxicology (2017)
Authors:
Obergrussberger A., Thomas U., Stölzle-Feix S., Becker N., Juhasz K, Doerr L., Beckler M., George M., Fertig N.
2016 - Myrsinane, Premyrsinane, and Cyclomyrsinane Diterpenes fromEuphorbia falcata as Potassium Ion Channel Inhibitors with Selective G Protein-Activated Inwardly Rectifying Ion Channel (GIRK) Blocking Effects
Patchliner publication in Journal of Natural Products (2016)
Authors:
Vasas A., Forgo P., Orvos P., Tálosi L., Csorba A., Pinke G., Hohmann J.
2016 - Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation
Patchliner publication in Journal of the American College of Cardiology (2016)
Authors:
Lorberbaum T., Sampson K.J., Chang J.B., Iyer V., Woosley R.L., Kass R.S., Tatonetti N.P.
2016 - Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Lab Automation (2016)
Authors:
Obergrussberger A., Brüggemann A., Goetze T.A., Rapedius M., Haarmann C., Rinke I., Becker N., Oka T., Ohtsuki A., Stengel T., Vogel M., Steindl J., Mueller M., Stiehler J., George M., Fertig N.
2015 - Novel screening techniques for ion channel targeting drugs
Patchliner, SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and CardioExcyte 96 publication in Channels (2015)
Authors:
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.
2015 - Electrophysiological analysis of mammalian cells expressing hERG using automated 384-well-patch-clamp
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in BCM Pharmacology and Toxicology (2015)
Authors:
Haraguchi Y., Ohtsuki A., Oka T., Shimizu T.
2014 - New strategies in ion channel screening for drug discovery: are there ways to improve its productivity?
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Laboratory Automation (2014)
Authors:
Farre C., Fertig N.
2014 - Early identification of hERG liability in drug discovery programs by automated patch clamp
Patchliner and SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Frontiers in Pharmacology (2014)
Authors:
Danker T., Moeller C.
2013 - Differential Effects of the β‐Adrenoceptor Blockers Carvedilol and Metoprolol on SQT1‐ and SQT2‐Mutant Channels
Port-a-Patch publication in Journal of Cardiovascular Electrophysiology (2013)
Authors:
Bodi I., Franke G., Pantulu N.D., Wu K., Perez-Feliz S., Bode C., Zehender M., Zur Hausen A., Brunner M., Odening K.
2012 - Toward a new gold standard for early safety: automated temperature-controlled hERG test on the Patchliner
Patchliner publication in Frontiers in Pharmacology (2012)
Authors:
Polonchuk L.
2012 - Synthesis and In Vitro Antibacterial Activity of Novel 3‐Azabicyclo [3.3. 0] octanyl Oxazolidinones
Patchliner publication in Chemical Biology and Drug Design (2012)
Authors:
Bhattarai D., Lee S.H., Seo S.H., Nam G., Kang S.B., Pae A.N., Kim E.E., Oh T., Cho S.N., Keum G.
2012 - Effects of the Antitussive Drug Cloperastine on Ventricular Repolarization in Halothane-Anesthetized Guinea Pigs
Port-a-Patch publication in Journal of Pharmacologigal Sciences (2012)
Authors:
Takahara A., Fujiwara K., Ohtsuki A., Oka T., Namekata I., Tanaka H.
2011 - State-of-the-art automated patch clamp devices: heat activation, action potentials, and high throughput in ion channel screening
Port-a-Patch, Patchliner and SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Frontiers in Pharmacology (2011)
Authors:
Stoelzle S., Obergrussberger A., Brüggemann A., Haarmann C., George M., Kettenhofen R., Fertig N.
2011 - Automated electrophysiology makes the pace for cardiac ion channel safety screening
Patchliner and SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Frontiers in Pharmacology (2011)
Authors:
Möller C., Witchel H.
2009 - Port-a-Patch and Patchliner: High fidelity electrophysiology for secondary screening and safety pharmacology
Port-a-Patch and Patchliner publication in Combinatorial Chemistry & High Throughput Screening (2009)
Authors:
Farre C., Haythornthwaite A., Haarmann C., Stoelzle S., Kreir M., George M., Brüggemann A., Fertig N.
2007 - Electrophysiological assessment of HERG blockade: Comparative study using automated and conventional patch clamp systems
Port-a-Patch publication in Toxicological Letters (2007)
Authors:
Yook Y., Kim J., Cho H., Moon H., Kwak B.
2005 - Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles
Port-a-Patch publication in Nano Letters (2005)
Authors:
Kirchner C., Liedl T., Kudera S., Pellegrino T., Munoz J. A., Gaub H.E., Stoelzle S., Fertig N., Parak W.J.