Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Piezo1 integration of vascular architecture with physiological force


This article has been updated


The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic1,2,3,4,5. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+-permeable non-selective cationic channels for detection of noxious mechanical impact6,7,8. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Piezo1 function in murine embryos.
Figure 2: Piezo1 in shear stress sensing.
Figure 3: The role of Piezo1 in endothelial cell alignment.
Figure 4: Piezo1 coupling to calpain.

Similar content being viewed by others

Change history

  • 12 November 2014

    Minor changes were made to the author list and author contributions.


  1. Conway, D. & Schwartz, M. A. Lessons from the endothelial junctional mechanosensory complex. F1000 Biol. Rep. 4, 1 (2012)

    PubMed  PubMed Central  Google Scholar 

  2. Chiu, J. J. & Chien, S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol. Rev. 91, 327–387 (2011)

    Article  Google Scholar 

  3. Ando, J. & Yamamoto, K. Flow detection and calcium signaling in vascular endothelial cells. Cardiovasc. Res. 99, 260–268 (2013)

    Article  CAS  Google Scholar 

  4. Mammoto, T. & Ingber, D. E. Mechanical control of tissue and organ development. Development 137, 1407–1420 (2010)

    Article  CAS  Google Scholar 

  5. Lucitti, J. L. et al. Vascular remodeling of the mouse yolk sac requires hemodynamic force. Development 134, 3317–3326 (2007)

    Article  CAS  Google Scholar 

  6. Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010)

    Article  ADS  CAS  Google Scholar 

  7. Coste, B. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, 176–181 (2012)

    Article  ADS  CAS  Google Scholar 

  8. Kim, S. E., Coste, B., Chadha, A., Cook, B. & Patapoutian, A. The role of Drosophila Piezo in mechanical nociception. Nature 483, 209–212 (2012)

    Article  ADS  CAS  Google Scholar 

  9. Olsson, A. K., Dimberg, A., Kreuger, J. & Claesson-Welsh, L. VEGF receptor signalling - in control of vascular function. Nature Rev. Mol. Cell Biol. 7, 359–371 (2006)

    Article  CAS  Google Scholar 

  10. Bae, C., Sachs, F. & Gottlieb, P. A. The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry 50, 6295–6300 (2011)

    Article  CAS  Google Scholar 

  11. Song, J. W. & Munn, L. L. Fluid forces control endothelial sprouting. Proc. Natl Acad. Sci. USA 108, 15342–15347 (2011)

    Article  ADS  CAS  Google Scholar 

  12. Dolan, J. M., Kolega, J. & Meng, H. High wall shear stress and spatial gradients in vascular pathology: a review. Ann. Biomed. Eng. 41, 1411–1427 (2013)

    Article  Google Scholar 

  13. Johnson, B. D., Mather, K. J. & Wallace, J. P. Mechanotransduction of shear in the endothelium: basic studies and clinical implications. Vasc. Med. 16, 365–377 (2011)

    Article  Google Scholar 

  14. Matthews, B. D., Overby, D. R., Mannix, R. & Ingber, D. E. Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J. Cell Sci. 119, 508–518 (2006)

    Article  CAS  Google Scholar 

  15. Tzima, E. et al. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437, 426–431 (2005)

    Article  ADS  CAS  Google Scholar 

  16. Brakemeier, S., Eichler, I., Hopp, H., Kohler, R. & Hoyer, J. Up-regulation of endothelial stretch-activated cation channels by fluid shear stress. Cardiovasc. Res. 53, 209–218 (2002)

    Article  CAS  Google Scholar 

  17. AbouAlaiwi, W. A. et al. Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ. Res. 104, 860–869 (2009)

    Article  CAS  Google Scholar 

  18. Hartmannsgruber, V. et al. Arterial response to shear stress critically depends on endothelial TRPV4 expression. PLoS ONE 2, e827 (2007)

    Article  ADS  Google Scholar 

  19. Yamamoto, K. et al. Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nature Med. 12, 133–137 (2006)

    Article  CAS  Google Scholar 

  20. Zarychanski, R. et al. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood 120, 1908–1915 (2012)

    Article  CAS  Google Scholar 

  21. Bae, C., Gnanasambandam, R., Nicolai, C., Sachs, F. & Gottlieb, P. A. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. Proc. Natl Acad. Sci. USA 110, E1162–E1168 (2013)

    Article  ADS  CAS  Google Scholar 

  22. Li, S. et al. The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells. Proc. Natl Acad. Sci. USA 99, 3546–3551 (2002)

    Article  ADS  CAS  Google Scholar 

  23. Langille, B. L. & Adamson, S. L. Relationship between blood flow direction and endothelial cell orientation at arterial branch sites in rabbits and mice. Circ. Res. 48, 481–488 (1981)

    Article  CAS  Google Scholar 

  24. Balligand, J. L., Feron, O. & Dessy, C. eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol. Rev. 89, 481–534 (2009)

    Article  CAS  Google Scholar 

  25. Lebart, M. C. & Benyamin, Y. Calpain involvement in the remodeling of cytoskeletal anchorage complexes. FEBS J. 273, 3415–3426 (2006)

    Article  CAS  Google Scholar 

  26. McHugh, B. J. et al. Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum. J. Cell Sci. 123, 51–61 (2010)

    Article  Google Scholar 

  27. Miyazaki, T., Honda, K. & Ohata, H. Requirement of Ca2+ influx- and phosphatidylinositol 3-kinase-mediated m-calpain activity for shear stress-induced endothelial cell polarity. Am. J. Physiol. Cell Physiol. 293, C1216–C1225 (2007)

    Article  CAS  Google Scholar 

  28. Arthur, J. S., Elce, J. S., Hegadorn, C., Williams, K. & Greer, P. A. Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division. Mol. Cell. Biol. 20, 4474–4481 (2000)

    Article  CAS  Google Scholar 

  29. Zhuang, X., Cross, D., Heath, V. L. & Bicknell, R. Shear stress, tip cells and regulators of endothelial migration. Biochem. Soc. Trans. 39, 1571–1575 (2011)

    Article  CAS  Google Scholar 

  30. Hahn, C. & Schwartz, M. A. Mechanotransduction in vascular physiology and atherogenesis. Nature Rev. Mol. Cell Biol. 10, 53–62 (2009)

    Article  CAS  Google Scholar 

  31. van Beijnum, J. R., Rousch, M., Castermans, K., van der Linden, E. & Griffioen, A. W. Isolation of endothelial cells from fresh tissues. Nature Protocols 3, 1085–1091 (2008)

    Article  CAS  Google Scholar 

  32. Wiśniewski, J. R., Zougman, A., Nagaraj, N. & Mann, M. Universal sample preparation method for proteome analysis. Nature Methods 6, 359–362 (2009)

    Article  Google Scholar 

  33. Thingholm, T. E., Jorgensen, T. J., Jensen, O. N. & Larsen, M. R. Highly selective enrichment of phosphorylated peptides using titanium dioxide. Nature Protocols 1, 1929–1935 (2006)

    Article  CAS  Google Scholar 

  34. Babaei, F. et al. Novel blood collection method allows plasma proteome analysis from single zebrafish. J. Proteome Res. 12, 1580–1590 (2013)

    Article  CAS  Google Scholar 

  35. Huang Da W, Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 4, 44–57 (2009)

    Article  Google Scholar 

  36. Warboys, C. M. et al. Disturbed flow promotes endothelial senescence via a p53-dependent pathway. Arterioscler. Thromb. Vasc. Biol. 34, 985–995 (2014)

    Article  CAS  Google Scholar 

  37. Rezakhaniha, R. et al. Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy. Biomech. Model. Mechanobiol. 11, 461–473 (2012)

    Article  CAS  Google Scholar 

Download references


The research was supported by research grants from the Wellcome Trust, the Medical Research Council, the Leeds Teaching Hospitals Trust Charitable Foundation, and the British Heart Foundation. B.H. was supported by a Scholarship from the University of Leeds and the China Scholarship Council. A.J.H. was supported by a BBSRC PhD Studentship. R.S.Y. was supported by a Cancer Research UK Clinical Fellowship. L.A.W. was supported by a BBSRC-AstraZeneca PhD Studentship. M.A.B. was supported by a British Heart Foundation Fellowship.

Author information

Authors and Affiliations



J.L. initiated the experimental studies of Piezo1 and was the primary contributor to experiments on endothelial cell tube formation, Piezo1 gene-modified mice and Piezo1 overexpression. B.H. initiated the experimental studies of shear stress and was the primary contributor to experiments on shear-stress-evoked Ca2+ responses, Piezo1 redistribution and Piezo1-dependence of endothelial cell alignment. J.L. and B.H. addressed the calpain hypothesis. S.T. initiated the proteomic experiments and nitric oxide synthase studies. K.M. performed patch-clamp experiments. A.S., R.S.Y., N.Y.Y., L.M.K, Y.M., L.A.W., B.R., A.B., M.J.L., A.J.H., D.A.L.C., J.B., P.A. and R.M.C. also contributed to experiments or prepared cells, mice or reagents. J.L., B.H., S.T., K.M., H.I., Z.F. and A.J.H. analysed data, interpreted data and developed methods. K.R.P. provided essential material. J.L., B.H., S.T., K.M., H.R.K., M.T.K., M.A.B., T.N.D., P.C.E. and J.F.X.A. provided intellectual input. All authors commented on the manuscript. D.J.B. initiated the project, generated research funds and ideas, led and coordinated the project, interpreted data and wrote the paper.

Corresponding author

Correspondence to David J. Beech.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (dataset identifier: PXD001099 and DOI 10.6019/PXD001099).

Extended data figures and tables

Extended Data Figure 1 Piezo1 mRNA in aorta and endothelial cells.

a, End-point PCR products obtained with Piezo1 primers for human (h.) liver and mouse (m.) lung endothelial cell (EC) and freshly dissected mouse aorta mRNA after reverse transcriptase reaction (RT) to generate cDNA. b, As for a but for human late outgrowth endothelial progenitor cells (LEPC) and 7 types of human endothelial cell (art., arterial; micr., microvascular; pul., pulmonary; umb., umbilical; car., cardiac; bla., bladder; der., dermal; col., colonic). Results are shown with (+ RT) and without (−RT) reverse transcription. c, Quantitative real-time PCR data for experiments of the type shown in a (n = 2 each in duplicate). d, Quantitative real-time PCR data for experiments of the type shown in b (n = 1 each in duplicate).

Source data

Extended Data Figure 2 Role of Piezo1 channels in HUVEC migration and tube formation.

a, Western blot for HUVEC lysate probed with anti-Piezo1 antibody after transfection with the control siRNA (, 2 different single Piezo1 siRNAs ( or, or a pooled set of Piezo1 siRNAs ( The upper band in the upper blot represents Piezo1 with a predicted mass of 286 kDa. The band immediately below is unknown protein labelled non-specifically by anti-Piezo1 antibody (*). The lower blot shows β-actin included as a protein-loading control. b, Another western blot for HUVEC lysate probed with anti-Piezo1 antibody after transfection with control siRNA ( or Piezo1 siRNA ( The arrow points to Piezo1 protein. Apparent depletion of an additional protein by is evident at about 130 kDa but this effect was not reproducible in other experiments. Other proteins (for example, at about 250(*), 190, and 100 kDa) were non-specifically labelled by the anti-Piezo1 antibody and not affected by Piezo1 siRNA. More specific anti-Piezo1 antibody could not be found. c, Normalized quantitative densitometry analysis for Piezo1 band of the type shown in b (n = 3). d, Specificity of depletion by Piezo1 siRNA. The effect of the TRPV4 channel activator 10 μM 4α-phorbol 12,13-didecanoate (4-αPDD) is shown on intracellular Ca2+ in HUVECs in multiple wells of a 96-well plate on a fluorescence plate-reader (representative of n = 3). HUVECs were transfected with or The data show that did not affect TRPV4. e, Cell migration after transfection with compared with or compared with (n = 4 each). f, As for e but comparing vehicle controls with 5 μM GsMTx4 or 30 μM ruthenium red (n = 3 each). g, Example images of in vitro tube formations in co-culture with fibroblasts. HUVECs were transfected with or and labelled with anti-CD31 antibody (green). Scale bar, 400 μm. h, Analysis of tube length in images of the type shown in g and similarly for (n = 3 for all groups). i, Example sections from in vivo Matrigel plugs in which HUVECs were transfected with or The arrow points to a typical tube structure. Scale bar, 50 μm. j, Mean data from tubes exemplified by i for 6 independent experiments (i–vi) (5–17 tissue sections each). Error bars are s.e.m.

Source data

Extended Data Figure 3 Global and endothelial-specific Piezo1 modification and embryonic growth retardation in mice.

a, Simplified diagram of the Piezo1 Knockout First (conditional) construct provided in ES cells by the KOMP Repository ( Piezo1 is indicated containing the insertion of lacZ sequence flanked by flippase recognition target (FRT) sites and downstream loxP sites. Further details of the construct can be obtained at ( b, c, Global modification. b, Example genotyping results with lacZ or loxP-spanning PCR primers. M indicates the DNA marker ladder. On the left are results for 6 mice analysed by the lacZ PCR primers (expected product: 225 bp). On the right are the results for the same 6 mice analysed by primers targeted to endogenous Piezo1 sequence either side of the 3′ terminal loxP site (expected products: 155 bp without the loxP site; 189 bp with the loxP site). In the gel shown, 3 mice were heterozygous for the construct (+/−), 2 homozygous (−/−), and 1 wild type (+/+). c, Images of example sibling E10.5 embryos. The embryo on the left was Piezo1+/+and the embryo on the right was Piezo1−/−. Scale bar, 1 mm. dg, Endothelial-specific modification. d, Example genotyping results for two mice (mouse 1 and mouse 2) both with deletion of the lacZ insert and transmission of Tie2-Cre. Controls for the absence and presence of lacZ, the loxP insert, and Tie2-Cre are included. Successful deletion of the lacZ insert was confirmed by lack of β-galactosidase staining (data not shown). e, Example genotyping results for six sibling embryos analysed with PCR primers spanning the deletion predicted to result from Cre recombinase activity at the loxP sites. The forward primer was 5′ of the 5′ FRT site illustrated in a and the reverse primer was 3′ of the 3′ loxP site. The PCR product size after deletion was expected to be 379 bp. The product was detected in embryos 2 and 6. The PCR product was not generated in embryos without the deletion because it was too long to be amplified (4,208 bp). Embryos exhibiting the 379 bp product were designated ‘EC-del.’ to indicate disruptive deletion in Piezo1 of endothelial cells (ECs). Embryos designated as wild type (wt.) exhibited no 379 bp product and only the 155 bp loxP product (as shown for the ‘no loxP insert control’ in d). Out of a total of 142 embryos, 57 were EC-del. f, RT–PCR products detecting Piezo1 mRNA in total RNA from sibling embryos (Piezo1 3′ PCR primers) (n = 3, each in duplicate). Piezo1 mRNA was significantly depleted in embryos displaying the 379 bp product described and shown in e. g, Images of example sibling E10.5 embryos. The embryo on the left was wild type and the embryo on the right contained the endothelial-specific Piezo1 deletion (EC-del.). Retarded growth was apparent in EC-del embryos and none of the other embryos. Scale bar, 1 mm. Error bars are s.e.m.

Source data

Extended Data Figure 4 Piezo1-dependence of shear-stress-evoked Ca2+ events in human endothelial cells and mouse embryonic endothelial cells.

a, Example intracellular Ca2+ events evoked by microfluidic shear stress in HUVECs transfected with control siRNA ( or ( Each trace is for 1 cell. In one cell, transient Ca2+ elevation remained. Such residual events may reflect insufficient Piezo1 depletion in some cells or non-Piezo1 mechanisms. b, Mean data for experiments of the type in a and expanded to paired comparisons of and (n = 5 each), and (n = 4 each), vehicle and 2.5 μM GsMTx4 (n = 3 each). Data were normalized to their respective controls. c, Quantification of Piezo1 mRNA depletion (n = 4 each) plotted against the inhibition of the intracellular Ca2+ elevations evoked by 20 dyn per cm2. Three different Piezo1 siRNAs were compared with their control siRNAs. The Ca2+ data are from the experiments described in b. Sequence details of the siRNAs are provided in Supplementary Table 3. d, Mean Ca2+ signals evoked by 20 dyn per cm2 in non-transfected HUVECs. Measurements were made in standard bath solution without the addition of an inhibitor (no inhibitor) (n = 8), 10 μM gadolinium chloride (Gd3+) (n = 3), or with Ca2+ omitted from the bath solution (0 Ca2+) (n = 3). e, Ca2+ release evoked by 2 μM thapsigargin (TG) in the absence of extracellular Ca2+ and after transfection with or (20 wells of a 96-well plate each). f, Mean data normalized to for experiments of the type shown in e and analysed for the rate of rise of the Ca2+ event evoked by TG (n = 3 each). g, Similar to b but endothelial cells were from patient liver samples, data were not normalized, and only was used (n = 3, 4, 10 and 5 for shear stresses of 5, 10, 15 and 20 dyn per cm2). h, i, Intracellular Ca2+ measurements from mouse embryonic endothelial cells in microfluidic chambers. h, Superimposition of example intracellular Ca2+ events in 2 single cells on different coverslips from Piezo1+/+ and Piezo1−/− sibling embryos. Shear stress was applied at 15 and 25 dyn per cm2 and then 30 ng ml−1 VEGF was introduced while maintaining shear stress at 25 dyn per cm2. i, Mean ± s.e.m. data for all VEGF-responsive cells studied as exemplified in h (n = 6 +/+, 54 cells; n = 5 −/−, 42 cells). The same data are summarized in simplified form in Fig. 2a. Error bars are s.e.m.

Source data

Extended Data Figure 5 Piezo1-dependence of mechanically activated single channels in HUVECs.

a, Example single channel currents in a cell-attached patch at three voltages without subtraction of holding current. Application of −15 mm Hg pressure steps to the patch pipette evoked open channel unitary currents that summated to two levels marked as O1 and O2. Closed channel current is indicated by C. b, Mean amplitudes of unitary events as exemplified in a and fitted with a straight line (3 patches for −50, −30 and −50 mV; 1 patch for +30 mV). c, Paired comparisons of the percentage of patches containing channel events exemplified in a for cells transfected with or in two independent experiment groups (n values for each group are in parentheses). In Group 2 cell-attached patch recordings cells were exposed for 10 min to 0.4 mM EGTA to chelate contaminating Ca2+ before recording so that and cells rounded up similarly; without this treatment (Group 1), but not cells tended to round up in response to the high-K+ bath solution used to null the membrane potential of cells in cell-attached patch recordings (the reason for this effect is unknown but it may relate to changes in cytoskeleton and adhesion as discussed in relation to Fig. 4). Error bars are s.e.m.

Source data

Extended Data Figure 6 Shear-stress-evoked redistribution of Piezo1 and the role of Piezo1 in alignment of endothelial cells to the direction of shear stress.

The application and direction of shear stress is indicated by open arrows and the cells were HUVECs. a, The left-hand image is of Piezo1–GFP in a single cell with a box indicating the region expanded in the middle and right-hand images after 0 and 50 min 15 dyn per cm2 in the microfluidic chamber. In the left image i indicates the part of the cell that became trailing after application of shear stress and ii that which became leading. Scale bars, 10 μm. b, Analysis of experiments of the type shown in a (n = 8 per data point except for n = 7 at 50 min) where i and ii indicate the trailing and leading edges of the cell as shown in a. c, Example cells after 24 h shear stress caused by the orbital shaker. Rhodamine phalloidin labelled F-actin (red) and DAPI labelled cell nuclei (blue). A paired comparison was made of cells transfected with control siRNA ( or Piezo1 siRNA ( Scale bars, 50 μm. d, Example orientation analysis for pairs of images of the type shown in c. e, As for d but normalized mean data for the frequency (number of angles) at the mode in experiments comparing mock with transfected cells (n = 5 each) and 2.5 μM GsMTx4 with its vehicle control (n = 4 each). There is also comparison of cells transfected with or after 15 h of 15 dyn per cm2 in the microfluidic chamber (n = 3). Error bars are s.e.m.

Source data

Extended Data Figure 7 Coupling to endothelial nitric oxide synthase.

a, Western blot for HUVEC lysates probed with anti-Piezo1 antibody after transfection with Piezo1 siRNA (on the left) or the control siRNA (on the right). Prior to collection of cell lysates, HUVECs were treated with 30 ng mL−1 VEGF (+) or no VEGF (−) for 10 min. The lysate was probed with anti-Piezo1 antibody, antibody to phosphorylated S1177 in eNOS, anti-β-actin antibody, and antibody to total eNOS protein. Positions of the expected proteins are indicated by the text on the right. The non-specific band at 250 kDa in the anti-Piezo1 blot is highlighted with *, as in Extended Data Fig. 2a, b. b, Quantitative data for the downregulation of total eNOS after transfection of HUVECs with (n = 6). c, Fold-change in S1177 eNOS phosphorylation (p-eNOS) evoked by VEGF (30 ng mL−1) in HUVECs transfected with control siRNA ( or Piezo1 siRNA ( (n = 3 each). The grey dashed line highlights 1-fold (that is, no change). d, Western blot for VEGF (30 ng mL−1) evoked S1177 eNOS phosphorylation (arrow) in aorta. Aorta was dissected from Piezo1+/+ or Piezo1+/− litter-mates and allowed to equilibrate at 37°C in culture medium without shear stress for 3 h. Aorta was then exposed to VEGF (30 ng mL−1) (+VEGF) or not (−VEGF) for 10 min, after which lysates were generated. Proteins were probed with antibody to phosphorylation at S1177 in eNOS. The band labelled with ** was not included in the analysis. The blot was also probed with anti-β-actin antibody to test for equal protein loading. e, Mean data for the type of experiment exemplified in d (n = 5 for each genotype) and presented as in c. f, Western blotting for HUVEC lysates after transfection with control siRNA ( or eNOS siRNAs. The blot was probed with anti-eNOS (total) antibody. g, HUVEC migration to VEGF after incubation with vehicle control, 0.3 mM l-NMMA for 0.5 h, or 48 h after transfection with or one of three siRNAs targeted to eNOS (n = 3 each; each paired to its own control). h, Data interpretation. Error bars are s.e.m.

Source data

Extended Data Figure 8 Endothelial cell alignment to shear stress lacks dependency on nitric oxide but is coupled to calpain.

a, Frequency of HUVEC alignment induced on the orbital shaker. Data for each test condition were normalized to their own control. Test conditions were 0.3 mM l-NMMA (n = 3) and transfection with eNOS siRNA ( compared with mock transfection (n = 4). b, Protein abundances from mass spectrometry analysis for the indicated proteins in 3 Piezo1−/− relative to 3 Piezo1+/+ E10.5 embryos. Calpain-2 and its substrates were less in Piezo1−/− embryos. The effects were relatively specific because more than 1,300 of the detected proteins were unchanged by Piezo1 depletion; data for 2 examples (myosin light chain-3 and integrin-β1) are shown. c, Fluorescence images of Piezo1–GFP in a HUVEC before (upper image) and after (lower image) 15 dyn per cm2 for 50 min. The small solid arrows point to focal adhesion structures at the trailing edge of the cell. Scale bar, 10 μm. Representative of n = 4. Error bars are s.e.m.

Source data

Supplementary information

Supplementary Tables

This file contains Supplementary Tables 1-3 (see separate excel files for Supplementary Tables 1 and 2). (PDF 165 kb)

Supplementary Data

This file contains relevant peptides for Supplementary Tables 1 and 2 that were significantly different (P<0.05) in compared with in HUVECs. (XLSX 16 kb)

Supplementary Data

This file shows calpain-substrate and calpain peptides that were significantly different (P<0.05) in Piezo1-/- compared with Piezo1+/+ at E10.5 for Supplementary Table 2. (XLSX 12 kb)

In vivo ultrasound to detect E9.5 embryonic heart beat

The embryo is on the left. (MOV 1643 kb)

In vivo ultrasound to detect E9.5 embryonic heart beat

Embryo with endothelial-specific deletion in Piezo1 (EC-del.) The embryo is on the right. (MOV 1644 kb)

PowerPoint slides

Source data

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Hou, B., Tumova, S. et al. Piezo1 integration of vascular architecture with physiological force. Nature 515, 279–282 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing