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Image Search Results
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Structural models of PIEZO1 and PIEZO2, showing the tag positions (magenta stars). b , Interblade distances for mouse PIEZO1 tagged at residue 103 (grey; n = 36 molecules, n = 4 cells) and PIEZO2 tagged at residue 105 (blue; n = 52 molecules, n = 4 cells) in unstimulated PtK2 cells. Kolmogorov–Smirnov test, **** P = 6.3 × 10 −5 , D = 0.44. c , The variance and 95% confidence intervals (CI) of the mean interblade distances in b . F test of equality of variances, P = 8.5 × 10 −8 , F = 5.6. d , PIEZO1 interblade distances from expansive membrane stretch (red; median = 34.7 nm; n = 41 molecules, n = 3 cells) versus unstimulated (grey; median = 26.5 nm). Kolmogorov–Smirnov test, * P = 0.01, D = 0.38. e , PIEZO2 during expansive membrane stretch (magenta; median: 18.9 nm; n = 53 molecules, n = 3 cells) versus unstimulated (blue; median = 19.9 nm). Kolmogorov–Smirnov test, * P = 0.01, D = 0.26. f , Current–voltage curves of hypo-osmotic-swelling-evoked current density for PIEZO1 ( n = 9 cells) and PIEZO2 ( n = 8 cells) in SWELL1 -KO HEK293 cells. The arrow denotes the current at +80 mV, used for quantification. g , Peak stretch-induced current density at +80 mV for f , including untransfected controls ( n = 7 cells). Kruskal–Wallis test with Dunn’s post hoc test, **** P = 6.2 × 10 −5 . h , PIEZO1 interblade distances from hyperosmotic stimulus (yellow; median = 19.8 nm; n = 21 molecules, n = 3 cells) versus unstimulated (grey). Kolmogorov–Smirnov test, ** P = 0.008, D = 0.46. i , PIEZO2 during hyperosmotic stimulus (green; median = 30.6 nm; n = 57 molecules, n = 3 cells). Kolmogorov–Smirnov test; **** P = 1.3 × 10 −9 , D = 0.54. j , Peak stretch-induced current from hyperosmotic stimulus in SWELL1 -KO HEK293 cells expressing PIEZO2 ( n = 8 cells) and untransfected controls ( n = 6 cells). Mann–Whitney U -test, P = 0.181. k , The peak induced current density from hyperosmotic stimulus in PtK2 control cells ( n = 6 cells) versus cells expressing PIEZO1 or PIEZO2 ( n = 7 cells each). Kruskal–Wallis test, ** P = 0.001. Data are mean ± s.d. ( b ), median ± 95% CI ( d , e , h and i ) and mean ± s.e.m. ( f , g , j and k ). All statistical tests were two-sided.
Article Snippet: Two
Techniques: Residue, Membrane, Expressing, MANN-WHITNEY, Control
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Schematic of DNA PAINT with traditional and fluorogenic DNA PAINT. A DNA docking strand is conjugated to the distal extracellular blade of PIEZO1 or PIEZO2. Traditional DNA PAINT imaging strands remain fluorescent in solution when not bound to the docking strand, but fluorogenic imaging strands are quenched, reducing background. b-c , PtK2 cells expressing mPIEZO1 TCO*K 103 imaged with 5 nM imaging strand, with and without a fluorescence quencher on the imaging strand. Imaging parameters were exactly the same (5% excitation power, 0.60 AU pinhole). Left, determined fluorescence background photon emission frequency in the sample. Middle, effective photon emission frequency at offset TCP position for the final iteration of a localization. Right, Number of localizations collected per trace. n = 2 cells per condition. d , Standard deviation per trace calculated in each dimension for unfiltered traces containing >10 localizations.
Article Snippet: Two
Techniques: Imaging, Expressing, Fluorescence, Standard Deviation
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Tether-coupled gating model: changes in membrane properties (for example, curvature) relative to a cytoskeletal tether exert force on the blade domains. b , Cytochalasin D (CytoD) decreases the resting PIEZO2 interblade distance (dark blue; median = 20.1 nm; n = 51 molecules, n = 3 cells; Kolmogorov–Smirnov test, **** P = 3.4 × 10 −5 , D = 0.40) and permits blade expansion from expansive membrane stretch (green; median = 28.3 nm; n = 24 molecules, n = 5 cells; Kolmogorov–Smirnov test, *** P = 0.0002, D = 0.53). c , CytoD enables stretch-evoked PIEZO2 activation in SWELL1 -KO HEK293 cells. n = 5 (control), n = 7 (PIEZO2) and n = 5 (PIEZO2 + CytoD) cells. Kruskal–Wallis test, * P = 0.048. d , Schematic of PIEZO2 blade expansion after actin disruption. e , PIEZO2(ΔIDR5) shows reduced interblade distance at rest (light blue; median = 16.6 nm; n = 30 molecules, n = 4 cells; Kolmogorov–Smirnov test, **** P = 9.7 × 10 −6 , D = 0.57) and robust expansion from hypo-osmotic swelling (orange; median = 37.2 nm; n = 21 molecules, n = 6 cells; Kolmogorov–Smirnov test, **** P = 3.9 × 10 −7 , D = 0.79). f , Hypo-osmotic swelling gates PIEZO2(ΔIDR5) in SWELL1 -KO cells. n = 5 (control), n = 10 (PIEZO2) and n = 4 (PIEZO2(ΔIDR5)). Kruskal–Wallis test, * P = 0.011. g , Schematic of PIEZO2(ΔIDR5) blade expansion from expansive membrane stretch. h , Overlaid MINFLUX single-molecule trajectories aligned by centre of mass (≥1 s) (top). Bottom, MSD analysis for trajectories with ≥200 localizations. Trajectories (grey) were averaged (50 bins in 350 ms; black circles) and fit at 5–50 ms (cyan, microscopic D : PIEZO1 = 0.0218, PIEZO2 = 0.0096, PIEZO2(ΔIDR5) = 0.0264 µm 2 s −1 ) and 50–350 ms (magenta, macroscopic D : PIEZO1 = 0.0197, PIEZO2 = 0.0041, PIEZO2(ΔIDR5) = 0.0149 µm 2 s −1 ). n = 55 (PIEZO1), n = 61 (PIEZO2) and n = 36 (PIEZO2(ΔIDR5)) trajectories. i , Diffusion coefficients from individual trajectories in h . Top, microscopic D for PIEZO2 (blue; median = 0.011 µm 2 s −1 ), PIEZO1 (grey; median = 0.024 µm 2 s −1 ) and PIEZO2 ΔIDR5 (dark blue; median = 0.032 µm 2 s −1 ). Kruskal–Wallis test, **** P = 3.8 × 10 −9 (PIEZO1 versus PIEZO2), **** P = 1.3 × 10 −14 (PIEZO2 versus PIEZO2(ΔIDR5)). n = 104 (PIEZO1), n = 87 (PIEZO2) and n = 65 (PIEZO2(ΔIDR5)) trajectories. Bottom, macroscopic D for PIEZO2 (blue circles; median = 0.011 µm 2 s −1 ), PIEZO1 (grey; median = 0.024 µm 2 s −1 ) and PIEZO2(ΔIDR5) (dark blue; median = 0.036 µm 2 s −1 ). Kruskal–Wallis test, ** P = 0.0023, **** P = 1.2 × 10 −9 . n = 55 (PIEZO1), n = 61 (PIEZO2) and n = 36 (PIEZO2(ΔIDR5)) trajectories. Data are mean ± s.e.m. ( c , f and h ) and median ± 95% CI ( b , e and i ). All statistical tests are two-sided. The diagrams in a , d and g were created using BioRender; Mulhall, E. M. https://BioRender.com/5k5114d (2026).
Article Snippet: Two
Techniques: Membrane, Activation Assay, Control, Disruption, Diffusion-based Assay
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Histograms of EFO (effective photon frequency measured at TCP offset) for each MINFLUX tracking experiment. The photon emission peaks corresponding to one dye (Peak 1) or two dyes (Peak 2) are noted. An upper EFO threshold of 150 kHz was applied to each dataset to eliminate signal arising from multiple dyes. b , Histograms of EFO for PIEZO1 measured with 0.5 nM dye (from Extended Data Fig. 5a) and 4 nM dye. Increased labelling concentration led to a disproportionate increase in the higher-frequency EFO peak (~ 150 kHz) relative to the single-molecule peak (~ 75 kHz), consistent with a higher fraction of multi-molecule events at higher labelling densities. c , Results from single-molecule tracking of the PIEZO1 + IDR5 chimera in which the fifth IDR of PIEZO1 (amino acids 551–575) was replaced with the corresponding IDR5 region from PIEZO2 (amino acids 620–672). Left, Ensemble Mean Squared Displacement (MSD) against time for trajectories containing at least 200 localizations fit between 5–50 ms (PIEZO1: D = 0.0218 µm 2 s −1 , PIEZO1 + IDR5: D = 0.0204 µm 2 s −1 ) and between 50–350 ms (PIEZO1: D = 0.0197 µm 2 s −1 , PIEZO1 + IDR5: D = 0.0153 µm 2 s −1 ). (n, trajectories: PIEZO1: n = 55, PIEZO1 + IDR5: n = 29). Error bars: mean ± SEM. Middle, microscale diffusion coefficients for PIEZO1 (grey circles; median = 0.024 µm 2 s −1 , n = 104), PIEZO1 + IDR5 (magenta circles; median = 0.022 µm 2 s −1 , n = 62), and PIEZO2 (blue circles; median = 0.011 µm 2 s −1 , n = 87). KW test: **** P = 2.0×10 −9 . Error bars: median ± 95% CI. Right, macroscale diffusion coefficients for PIEZO1 (grey circles; median = 0.024 µm 2 s −1 , n = 55), PIEZO1 + IDR5 (magenta circles; median = 0.018 µm 2 s −1 , n = 29), and PIEZO2 (blue circles; median = 0.011 µm 2 s −1 , n = 61). KW test: ** P = 0.0027. Error bars: median ± 95% CI. All statistical tests are two-sided.
Article Snippet: Two
Techniques: Concentration Assay, Diffusion-based Assay
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , The cross-linking MS workflow. LC, liquid chromatography. b , The exponentially modified protein abundance index (emPAI) ratio of proteins cross-linked to PIEZO2 versus PIEZO2(ΔIDR5). Candidate cytoskeletal–membrane tethers highlighted (magenta). c , Stretch-induced current in SWELL1 -KO HEK293 cells expressing PIEZO2 with non-targeting siRNA ( n = 46), FLNB siRNA ( n = 24) or other candidate siRNAs ( VINC ( n = 7), MOES ( n = 11), CTNB1 ( n = 10), FLNA ( n = 9) and TAGL2 ( n = 11)). d , Stretch-induced current in SWELL1 -KO HEK293 cells electroporated with scrambled CRISPR sgRNA (untransfected or expressing PIEZO2; n = 4 cells each) compared with clonal SWELL1 -KO/ FLNB -KO cells (untransfected ( n = 4) or expressing PIEZO2 ( n = 8)). Mann–Whitney U -test, ** P = 0.004. e , The PIEZO2 interblade distance in WT PtK2 cells (blue; median = 18.0 nm; n = 30 molecules, n = 4 cells) versus PtK2 cells with Potoroo Flnb DsiRNA (cyan; median = 16.8 nm; n = 41 molecules, n = 3 cells; Kolmogorov–Smirnov test, **** P = 4.5 × 10 −7 , D = 0.79) versus PtK2 cells with Flnb DsiRNA + hypo-osmotic swelling (purple; median = 37.0 nm; n = 39 molecules, n = 3 cells; Kolmogorov–Smirnov test, **** P = 3.2 × 10 −10 , D = 0.51). f , Schematic of expansive stretch without FLNB. g , MINFLUX tracking MSD fits: 5–50 ms (cyan, PIEZO2 + non-targeting DsiRNA: D = 0.0106 µm 2 s −1 ; PIEZO2 + Flnb DsiRNA: D = 0.0181 µm 2 s −1 ) and 50–350 ms (magenta, PIEZO2 + non-targeting DsiRNA: D = 0.00495 µm 2 s −1 ; PIEZO2 + Flnb DsiRNA: D = 0.0090 µm 2 s −1 ). n = 55 (PIEZO1), n = 61 (PIEZO2), n = 81 (PIEZO2 Flnb DsiRNA) and n = 50 (PIEZO2 NT DsiRNA) trajectories. h , Microscopic D from individual trajectories. n = 104 (PIEZO1), n = 87(PIEZO2), n = 126 (PIEZO2 Flnb DsiRNA) and n = 138 (PIEZO2 + non-targeting DsiRNA) trajectories. Kruskal–Wallis test, **** P = 2.1 × 10 −10 . i , Macroscopic D from individual trajectories. n = 55(PIEZO1), n = 61 (PIEZO2), n = 81 (PIEZO2 Flnb DsiRNA) and n = 50 (PIEZO2 non-targeting DsiRNA) trajectories. Kruskal–Wallis test, * P = 0.0183. j , Indentation-evoked current in SWELL1 -KO cells. n = 26 (PIEZO2), n = 7 (PIEZO2(ΔIDR5)) and n = 20 (PIEZO2 FLNB KO) cells. k , The indentation threshold for macroscopic current from j . Kruskal–Wallis test, * P = 0.0214, *** P = 0.0002. The box plots show the median (centre line), interquartile range (box limits, 25th–75th percentiles) and the minimum and maximum values (whiskers). l , Measured PIEZO2 blade conformation relative to cryo-EM (18.04 nm). For PIEZO2 + latrunculin A, median = 16.9 nm; n = 18 molecules, n = 4 cells; other values and n are described in Figs. , and 3e. Data are mean ± s.e.m. ( c , d , g , j and k ) and median ± 95% CI ( e , h , i and l ). All statistical tests were two-sided. The diagrams in a and f were created using BioRender; Mulhall, E. M. https://BioRender.com/5k5114d (2026).
Article Snippet: Two
Techniques: Liquid Chromatography, Modification, Quantitative Proteomics, Membrane, Expressing, CRISPR, MANN-WHITNEY, Cryo-EM Sample Prep
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Top, overlaid trajectories of PIEZO molecules from single molecule tracking with MINFLUX aligned by centre of mass for trajectories lasting at least 1 s for PtK2 cells expressing PIEZO2 with non-targeting DsiRNA. Bottom, Mean Squared Displacement against time for trajectories containing at least 200 localizations for the trajectories shown in Fig. . n = 50 trajectories. b , Top, overlaid single-molecule trajectories for cells expressing PIEZO2 with Flnb DsiRNA. Bottom, Mean Squared Displacement against time for trajectories shown in Fig. . n = 81 trajectories. Error bars: mean ± SEM ( a , b ).
Article Snippet: Two
Techniques: Expressing
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Quantification of the peak indentation-evoked current for the data in Fig. . Piezo2: 183.5 ± 42.1 pA/pF, n = 19 cells; Piezo2 Flnb KO: 90.2 ± 20.7 pA/pF, n = 19 cells; Piezo2 ΔIDR5: 59.0 ± 22.3 pA/pF, n = 7 cells. KW test: ** P = 0.0015, *** P = 0.0010. b , Indentation threshold to elicit a macroscopic current from Piezo1 in Swell1 KO and Swell1 KO + Flnb KO cells (n = 7 cells each). Mann-Whitney test: P = 0.5897. Box plot shows median (centre line) and interquartile range (box, 25th–75th percentiles); whiskers indicate minimum and maximum. c , Peak indentation-evoked current from Piezo1 in Swell1 KO and Swell1 KO + Flnb KO cells. Piezo1: 327.4 ± 123.8 pA/pF, n = 7 cells; Piezo2 Flnb KO: 397.4 ± 150.2 pA/pF, n = 7 cells. Mann-Whitney test: P = 0.2593. d , Amplitude of stretch-induced currents from osmotic swelling for untransfected Swell1 KO cells (−1.9 ± 0.6 pA/pF, n = 11 cells), Swell1 KO cells transfected with Piezo1 (14.6 ± 4.9 pA/pF, n = 9 cells), and Swell1 + Flnb KO cells transfected with Piezo1 (15.5 ± 4.5 pA/pF, n = 12 cells). KW test: ****P = 0.0002. Error bars in a , c , and d are mean ± SEM. All statistical tests are two-sided.
Article Snippet: Two
Techniques: MANN-WHITNEY, Transfection
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Representative images (11 images from 2 mice) of smFISH on sectioned mouse DRG for Ntrk2 , Flnb , Piezo2 and merged with DAPI. Yellow outlines indicate Ntrk2 + cells. Scale bar = 100 μm. b , Quantification of DRG smFISH images with the percentage of Ntrk2 + cells expressing Piezo2 , Flnb , or both. The number of co-expressing neurons is above the bar. c , Representative images (11 images from 2 mice) of sectioned mouse DRG smFISH for Ntrk3 , Flnb , Piezo2 and merged with DAPI. Scale bar = 100 μm. d , Quantification of DRG smFISH images with the percentage of Ntrk3 + cells expressing Piezo2 , Flnb , or both. e , Overview of lanceolate ROI assignment for the hair follicle shown in Fig. . f , Pearson’s correlation coefficient ( r = 0.54 ± 0.16) for the α-PIEZO2-FLAG and α-FLNB channels of the representative segmented lanceolate ROIs for the hair follicle in e . n = 16 lanceolates from 1 representative image. g , Spearman’s rank correlation coefficient for the same ROIs (ρ = 0.75 ± 0.08). Error bars are mean ± SD. n = 16 lanceolates from 1 representative image.
Article Snippet: Two
Techniques: Expressing
Journal: Nature
Article Title: The molecular basis of force selectivity by PIEZO2
doi: 10.1038/s41586-026-10182-7
Figure Lengend Snippet: a , Representative images of sectioned skin from Piezo2 smFP-Flag mice that contain end-organs formed by Ntrk2 + and/or Ntrk3 + LTMRs: lanceolate endings around hair follicles from back skin (top, five sections from two mice) and Meissner corpuscles from glabrous skin of paw digits (bottom, six sections from one mouse). Each section was co-stained with antibodies against NFH, PIEZO2–Flag and FLNB. Scale bars, 10 μm. b , Representative super-resolution STED microscopy image of PIEZO2–Flag and FLNB immunostaining in lanceolate endings showing co-localization of single puncta (six sections from two mice). Scale bars, 10 μm. c , Isolated single lanceolates from the yellow boxes in b (representative images of six sections from two mice). Scale bars, 500 nm. d , FWHM resolution of all identified peaks. Mean ± s.d. FWHM: anti-PIEZO2–Flag = 83 ± 31 nm, anti-FLNB = 62 ± 19 nm. n = 201(PIEZO2) and n = 469 (FLNB) puncta. e , Quantification of colocalization using Spearman’s rank correlation value ρ = 0.72 ± 0.12 (mean ± s.d.). n = 50 lanceolates from 5 follicles and 2 mice. f , The amplitude of stretch-induced currents in dissociated large diameter (≥70 µm) DRG neurons without any treatment (control, n = 8 cells), nucleofected with non-targeting DsiRNA ( n = 8 cells) or nucleofected with DsiRNAs targeting Flnb ( n = 9 cells). n = 3 mice for each condition. Two-sided Kruskal–Wallis test with Dunn’s multiple-comparison test; P = 0.9999 (control versus non-targeting DsiRNA), * P = 0.0105 (control versus Flnb DsiRNA), * P = 0.0201 (non-targeting DsiRNA versus Flnb DsiRNA).
Article Snippet: Two
Techniques: Staining, Microscopy, Immunostaining, Isolation, Control, Comparison
Journal: Nature Communications
Article Title: microRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism
doi: 10.1038/ncomms14395
Figure Lengend Snippet: ( a ) Pkd2 -KO mice were injected with 20 mg kg −1 of anti-miR-17 compound or PBS on postnatal day (P) 21, 22 and 23, and kidneys were harvested on P26. Kidney sections were co-stained with DBA (green, a marker of collecting ducts) and anti-PS antibody (red, antibody labels anti-miR-17 compound). Anti-PS staining was observed in collecting duct-derived cysts (arrowheads) of Pkd2 -KO mice injected with anti-miR-17 indicating that the compound was delivered to collecting duct cysts. No anti-PS antibody staining was noted in Pkd2 -KO mice injected with PBS. To assess the therapeutic efficacy of this compound, Pkd2 -KO mice were injected with anti-miR-17 or PBS at P10, 11, 12 and 19, and kidneys were harvested on P28. ( b ) H&E staining of kidney sections from 28-day-old Pkd2 -KO mice injected with anti-miR-17 or PBS. ( c ) Serum BUN levels, ( d ) kidney-weight-to-body-weight ratio, ( e ) expression of Kim1 and Ngal and ( f ) the number of proliferating cyst epithelial cells were reduced in Pkd2 -KO mice that were injected with anti-miR-17 compared with PBS. ( g – i ) To assess the therapeutic efficacy of anti-miR-17 in a long-term PKD model, 1-month-old Nphp3 pcy/pcy mice were injected with 50 mg kg −1 of anti-miR-17 or PBS once a week for 26 weeks. These mice were euthanized at 30 weeks of age. ( g ) Representative images of H&E-stained kidney sections from 30-week-old Nphp3 pcy/pcy mice injected with PBS or anti-miR-17 are shown. ( h ) kidney-weight-to-body-weight ratios and ( i ) cyst index were reduced in Nphp3 pcy/pcy mice that were injected with anti-miR-17 compared with PBS. Error bars represent s.e.m. Student's unpaired t -test ( c – f , h , i ). Scale bars, 25 μm ( a ) and 1 mm ( b ).
Article Snippet:
Techniques: Injection, Staining, Marker, Derivative Assay, Drug discovery, Expressing