flexcell品牌FX-6000T細(xì)胞牽張拉伸應(yīng)力加載系統(tǒng)(Flexcell FX6000 Tension system)

2D/3D細(xì)胞或組織靜態(tài)或動(dòng)態(tài)牽張等邊軸或單軸向牽張應(yīng)變加載和實(shí)時(shí)觀察
新增不用基底硬度牽張

亮點(diǎn)：

適用樣品：細(xì)胞或者組織（2D、3D）
軸向：二維等邊軸、二維單軸向、三維等邊軸、三維單軸向、三維梯形牽張
牽張模式：真空動(dòng)力抻拉培養(yǎng)板彈性柔性基底膜或3D水凝膠包埋的細(xì)胞
實(shí)時(shí)觀察：StageFlexer顯微附屬設(shè)備可在顯微鏡下觀察牽張作用下反應(yīng)
方便對照：可控制同一塊培養(yǎng)板部分孔細(xì)胞受力與否
多組牽張條件作用對照：可同時(shí)運(yùn)行多個(gè)不同壓力大小、不同頻率
不同加載周期程序，方便多組牽張條件對比；
軟件精準(zhǔn)調(diào)控：對牽張加載周期、張應(yīng)變大小、頻率、波形智能調(diào)控
牽張范圍：0 - 33%
牽張頻率：0.01- 5 Hz
細(xì)胞量大，便于后期分析：系統(tǒng)牽張傳導(dǎo)儀支持4塊6孔
（每孔1.2* 105個(gè)細(xì)胞）或24孔牽張板，可同時(shí)兼容4個(gè)獨(dú)立
的FlexLink牽張加載傳導(dǎo)儀 ，獨(dú)立操作四個(gè)不同的實(shí)驗(yàn)程序
支持任何波形種類：如更好地控制在超低或超高應(yīng)力下形：

細(xì)胞牽張受力同時(shí)可在倒置、正置顯微鏡下實(shí)時(shí)觀察細(xì)胞受力變化和反應(yīng)。

CellSoft不同硬度基底培養(yǎng)板可以在彈性模量范圍1-80kPa范圍內(nèi)牽張

典型應(yīng)用:

該系統(tǒng)感應(yīng)各種細(xì)胞在應(yīng)力刺激下的生物化學(xué)反應(yīng)，例如：骨骼細(xì)胞，肺細(xì)胞，心肌細(xì)胞，血細(xì)胞，皮膚細(xì)胞，
肌腱細(xì)胞，韌帶細(xì)胞，軟骨細(xì)胞和骨細(xì)胞等各種2D或3D細(xì)胞組織。
典型應(yīng)用科室:

CellSoft™ 培養(yǎng)板

•彈性模量范圍1-80kPa

•可選多孔板、60mm和100mm培養(yǎng)板

•BioFlex® CellSoft™ 標(biāo)準(zhǔn)6孔板

•在柔性基底上牽拉細(xì)胞

•腔室載玻片CellSoft™

•表面蛋白包被，無菌單獨(dú)包裝

CellSoft™ 培養(yǎng)板有很多不同的種類，如不同的硬度，不同的孔板，用于顯微觀察的腔室載玻片（圓形多孔板），共價(jià)包被Collagen I或其他蛋白，可對細(xì)胞進(jìn)行靜態(tài)或動(dòng)態(tài)牽拉應(yīng)力刺激。更重要的一點(diǎn)，新型的CellSoft™ 培養(yǎng)板可以反復(fù)胰酶消化和再接種細(xì)胞，蛋白包被的表面可以重復(fù)使用多達(dá)三次。

CellSoft不同硬度基底牽張文獻(xiàn)：

Key References:

Buxboim et al., How deeply do cells feel:methods for thin gels. J Phys Condens matter. 22: 1-19, 2010.

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Chodhury et al., Soft substrates promote homogeneous self-renewal of embryonic stem cells via down regulating cell-matrix tractions. PLOS 1 5: 1-10, 2010.

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Engle et al., Matrix elasticity directs stem cell lineage specification. Cell 126: 677-689, 2006.

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Hirata and Yamaoka. Effect of stem cell niche elasticity/ECM protein on the self-beating cardiomyocyte differentiation of iPS cells at different stages. Acta Biomat. 65: 44-52, 2018

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Megone et al., Impact of surface adhesion and sample heterogeneity on the multiscale mechanical characterization of soft biomaterials. Sci Rep 8: 6780, 2018.

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Ou et al., Visualizing mechanical modulation of nanoscale organization of cell-matrix adhesions. Integr. Biol. 8: 795-804,2016.

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Palchesko et al., Development of polydimethylsiloxane substrates with tunable elastic modulus to study cell mechanobiology in muscle and nerve. PLOS 1 7: 1-13, 2012

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Smith et al., Mechanosensing of matrix by stem cells: from matrix heterogeneity, contractility and the nucleus in pore-migration to cardiogenesis and muscle stem cells in vivo. Sem Cell Devtbio. 71: 84-98, 2017

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Solon et al., Fibroblast adaptation andstiffness matching to soft elastic substrates. Biophys J. 93: 4453-4461, 2007.

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Thomas et al., Measuring the mechanical properties of living cells using atomic force microscopy. J Visual Exp. 76:1-8, 2013.

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Vertelov et al., Rigidity of silicone substrates controls cell spreading and stem cell differentiation. Sci Rep. 6:1-10, 2016.

flexcell tension system應(yīng)用文獻(xiàn)：

BLADDER
BLADDER SMOOTH MUSCLE CELLS
1. Adam RM, Eaton SH, Estrada C, Nimgaonkar A, Shih SC, Smith LE, Kohane IS, Bagli D, Freeman MR. Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells. Physiol Genomics 20(1):36-44, 2004.
2. Adam RM, Roth JA, Cheng HL, Rice DC, Khoury J, Bauer SB, Peters CA, Freeman MR. Signaling through PI3K/Akt mediates stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells. J Urol 169(6):2388-2393, 2003.
3. Aitken KJ, Block G, Lorenzo A, Herz D, Sabha N, Dessouki O, Fung F, Szybowska M, Craig L, Bagli DJ. Mechanotransduction of extracellular signal-regulated kinases 1 and 2 mitogen-activated protein kinase activity in smooth muscle is dependent on the extracellular matrix and regulated by matrix metalloproteinases. Am J Pathol 169(2):459-470, 2006.
4. Aitken KJ, Tolg C, Panchal T, Leslie B, Yu J, Elkelini M, Sabha N, Tse DJ, Lorenzo AJ, Hassouna M, Bägli DJ. Mammalian target of rapamycin (mTOR) induces proliferation and de-differentiation responses to three coordinate pathophysiologic stimuli (mechanical strain, hypoxia, and extracellular matrix remodeling) in rat bladder smooth muscle. Am J Pathol 176(1):304-319, 2010.
5. Chaqour B, Yang R, Sha Q. Mechanical stretch modulates the promoter activity of the profibrotic factor CCN2 through increased actin polymerization and NF-?B activation. J Biol Chem 281(29):20608-20622, 2006.
6. Estrada CR, Adam RM, Eaton SH, Bägli DJ, Freeman MR. Inhibition of EGFR signaling abrogates smooth muscle proliferation resulting from sustained distension of the urinary bladder. Lab Invest 86(12):1293-1302, 2006.
7. Galvin DJ, Watson RW, Gillespie JI, Brady H, Fitzpatrick JM. Mechanical stretch regulates cell survival in human bladder smooth muscle cells in vitro. Am J Physiol Renal Physiol 283(6):F1192-F1199, 2002.
8. Halachmi S, Aitken KJ, Szybowska M, Sabha N, Dessouki S, Lorenzo A, Tse D, Bagli DJ. Role of signal transducer and activator of transcription 3 (STAT3) in stretch injury to bladder smooth muscle cells. Cell Tissue Res 326(1):149-158, 2006.
9. Hubschmid U, Leong-Morgenthaler PM, Basset-Dardare A, Ruault S, Frey P. In vitro growth of human urinary tract smooth muscle cells on laminin and collagen type I-coated membranes under static and dynamic conditions. Tissue Engineering 11(1-2):161-171, 2005.
10. Kushida N, Kabuyama Y, Yamaguchi O, Homma Y. Essential role for extracellular Ca2+ in JNK activation by mechanical stretch in bladder smooth muscle cells. Am J Physiol Cell Physiol 281(4):C1165-C1172, 2001.
11. Nguyen HT, Adam RM, Bride SH, Park JM, Peters CA, Freeman MR. Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells. Am J Physiol Cell Physiol 279(4):C1155-C1167, 2000.
12. Orsola A, Adam RM, Peters CA, Freeman MR. The decision to undergo DNA or protein synthesis is determined by the degree of mechanical deformation in human bladder muscle cells. Urology 59(5):779-783, 2002.
13. Orsola A, Estrada CR, Nguyen HT, Retik AB, Freeman MR, Peters CA, Adam RM. Growth and stretch response of human exstrophy bladder smooth muscle cells: molecular evidence of normal intrinsic function. BJU Int 95(1):144-148, 2005.
14. Park JM, Adam RM, Peters CA, Guthrie PD, Sun Z, Klagsbrun M, Freeman MR. AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells. Am J Physiol Cell Physiol 277:C294-C301, 1999.
15. Park JM, Borer JG, Freeman MR, Peters CA. Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells. Am J Physiol Cell Physiol 275:C1247-C1254, 1998.
16. Park JM, Yang T, Arend LJ, Schnermann JB, Peters CA, Freeman MR, Briggs JP. Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch. Am J Physiol Renal Physiol 276:F129-F136, 1999.
17. Persson K, Sando JJ, Tuttle JB, Steers WD. Protein kinase C in cyclic stretch-induced nerve growth factor production by urinary tract smooth muscle cells. Am J Physiol Cell Physiol 269:C1018-C1024, 1995.
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18. Steers WD, Broder SR, Persson K, Bruns DE, Ferguson JE 2nd, Bruns ME, Tuttle JB. Mechanical stretch increases secretion of parathyroid hormone-related protein by cultured bladder smooth muscle cells. J Urol 160(3 Pt 1):908-912, 1998.
19. Upadhyay J, Aitken KJ, Damdar C, Bolduc S, Bagli DJ. Integrins expressed with bladder extracellular matrix after stretch injury in vivo mediate bladder smooth muscle cell growth in vitro. J Urol 169(2):750-755, 2003.
20. Wang Y, Xiong Z, Gong W, Zhou P, Xie Q, Zhou Z, Lu G. Expression of heat shock protein 27 correlates with actin cytoskeletal dynamics and contractility of cultured human bladder smooth muscle cells. Exp Cell Res 338(1):39-44, 2015.
21. Yang R, Amir J, Liu H, Chaqour B. Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis. Physiol Genomics 36(1):1-14, 2008.
22. Yu G, Bo S, Xiyu J, Enqing X. Effect of bladder outlet obstruction on detrusor smooth muscle cell: an in vitro study. Journal of Surgical Research 114(2):202-209, 2003.
23. Zhou D, Herrick DJ, Rosenbloom J, Chaqour B. Cyr61 mediates the expression of VEGF, ?v-integrin, and ?-actin genes through cytoskeletally based mechanotransduction mechanisms in bladder smooth muscle cells. J Appl Physiol 98(6):2344-2354, 2005.
UROTHELIAL & UROEPITHELIAL CELLS
24. Jerde TJ, Mellon WS, Bjorling DE, Nakada SY. Evaluation of urothelial stretch-induced cyclooxygenase-2 expression in novel human cell culture and porcine in vivo ureteral obstruction models. J Pharmacol Exp Ther 317(3):965-972, 2006.
25. Jerde TJ, Mellon WS, Bjorling DE, Checura CM, Owusu-Ofori K, Parrish JJ, Nakada SY. Stretch induction of cyclooxygenase-2 expression in human urothelial cells is calcium- and protein kinase C ?-dependent. Mol Pharmacol 73(1):18-26, 2008. Erratum in: Mol Pharmacol 74(2):539, 2008.
26. Sun Y, Chai TC. Effects of dimethyl sulphoxide and heparin on stretch-activated ATP release by bladder urothelial cells from patients with interstitial cystitis. BJU Int 90(4):381-385, 2002.
27. Sun Y, Chai TC. Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. J Urol 171(1):448-452, 2004.
28. Sun Y, Keay S, De Deyne PG, Chai TC. Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. Journal of Urology 166(5):1951-1956, 2001.
29. Sun Y, Keay S, DeDeyne P, Chai T. Stretch-activated release of adenosine triphosphate by bladder uroepithelia is augmented in interstitial cystitis [abstract]. Urology 57(6 Suppl 1):131, 2001.
30. Sun Y, MaLossi J, Jacobs SC, Chai TC. Effect of doxazosin on stretch-activated adenosine triphosphate release in bladder urothelial cells from patients with benign prostatic hyperplasia. Urology 60(2):351-356, 2002.
BONE
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2. Aguirre JI, Plotkin LI, Gortazar AR, Millan MM, O'Brien CA, Manolagas SC, Bellido T. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J Biol Chem 282(35):25501–25508, 2007.
3. Bellido T, Plotkin LI. Detection of apoptosis of bone cells in vitro. Methods in Molecular Biology, Vol. 455: Osteoporosis: Methods and Protocols. Edited by Westendorf JJ. Humana Press: Totowa, 51-75, 2008.
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5. Boutahar N, Guignandon A, Vico L, Lafage-Proust MH. Mechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 tyrosine sites involved in ERK activation. J Biol Chem 279(29):30588-30599, 2004.
6. Buckley MJ, Banes AJ, Jordan RD. The effects of mechanical strain on osteoblasts in vitro. J Oral Maxillofac Surg 48(3):276-282, 1990.
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7. Buckley MJ, Banes AJ, Levin LG, Sumpio BE, Sato M, Jordan R, Gilbert J, Link GW, Tran Son Tay R. Osteoblasts increase their rate of division and align in response to cyclic, mechanical tension in vitro. Bone Miner 4(3):225-236, 1988.
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10. Carvalho RS, Scott JE, Yen EH. The effects of mechanical stimulation on the distribution of ?1 integrin and expression of ?1-integrin mRNA in TE-85 human osteosarcoma cells. Arch Oral Biol 40(3):257-264, 1995.
11. Case N, Ma M, Sen B, Xie Z, Gross TS, Rubin J. ?-catenin levels influence rapid mechanical responses in osteoblasts. J Biol Chem 283(43):29196-29205, 2008.
12. Chen X, Macica CM, Ng KW, Broadus AE. Stretch-induced PTH-related protein gene expression in osteoblasts. J Bone Miner Res 20(8):1454-61, 2005.
13. Chen YJ, Chang MC, Yao CC, Lai HH, Chang J, Jeng JH. Mechanoregulation of osteoblast-like MG-63 cell activities by cyclic stretching. J Formos Med Assoc 113(7):447-53, 2014.
14. Chung E, Sampson AC, Rylander MN. Influence of heating and cyclic tension on the induction of heat shock proteins and bone-related proteins by MC3T3-E1 cells. Biomed Res Int 2014:354260, 2014.
15. Cillo JE Jr, Gassner R, Koepsel RR, Buckley MJ. Growth factor and cytokine gene expression in mechanically strained human osteoblast-like cells: implications for distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90(2):147-154, 2000.
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18. Fan X, Rahnert JA, Murphy TC, Nanes MS, Greenfield EM, Rubin J. Response to mechanical strain in an immortalized pre-osteoblast cell is dependent on ERK1/2. J Cell Physiol 207(2):454-460, 2006.
19. Faure C, Linossier MT, Malaval L, Lafage-Proust MH, Peyroche S, Vico L, Guignandon A. Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation. Bone 42(6):1092-1101, 2008.
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25. Granet C, Vico AG, Alexandre C, Lafage-Proust MH. MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells. Cellular Signaling 14(8):679-688, 2002.
26. Grimston SK, Screen J, Haskell JH, Chung DJ, Brodt MD, Silva MJ, Civitelli R. Role of connexin43 in osteoblast response to physical load. Ann N Y Acad Sci 1068:214-224, 2006.
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29. Han L, Zhang X, Tang G. Indian Hedgehog signaling is involved in the stretch induced proliferation of osteoblast. Hua Xi Kou Qiang Yi Xue Za Zhi 30(3):234-8, 2012.
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30. Hara F, Fukuda K, Asada S, Matsukawa M, Hamanishi C. Cyclic tensile stretch inhibition of nitric oxide release from osteoblast-like cells is both G protein and actin-dependent. Journal of Orthopaedic Research 19(1):126-131, 2001.
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37. Karasawa Y, Tanaka H, Nakai K, Tanabe N, Kawato T, Maeno M, Shimizu N. Tension force downregulates matrix metalloproteinase expression and upregulates the expression of their inhibitors through MAPK signaling pathways in MC3T3-E1 cells. Int J Med Sci 12(11):905-13, 2015.
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44. Li Y, Tang L, Duan Y, Ding Y. Upregulation of MMP-13 and TIMP-1 expression in response to mechanical strain in MC3T3-E1 osteoblastic cells. BMC Res Notes 3:309, 2010.
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endothelial growth factor (VEGF) and macrophage-colony-stimulating factor (M-CSF) in murine osteoblastic MC3T3-E1 cells. J Dent Res 84(5):422-427, 2005.
51. Myers KA, Rattner JB, Shrive NG, Hart DA. Osteoblast-like cells and fluid flow: cytoskeleton-dependent shear sensitivity. Biochem Biophys Res Commun 364(2):214-219, 2007.
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