LINC复合体与细胞内机械力传导
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摘要
细胞作为力学感受器,可以感知、传递施加在其表面的机械力并调整自身力学性能,维持自身稳定。机械力从细胞表面或细胞质传递到细胞核依赖于完整的细胞骨架系统,该系统包括细胞质骨架和细胞核骨架两部分,而LINC复合体则是两者实现机械连接的桥梁,因此其在细胞内机械力传导中发挥着重要作用。综述LINC复合体传导机械力的结构基础和机械力传导引起的细胞核形态、转录因子的出入核以及染色质的空间构象的改变,为进一步探讨LINC复合体在细胞机械力传导过程中的作用及其对基因表达的影响奠定基础。
As mechanoreceptors, cells can sense and transmit mechanical forces exerted on their surfaces, meanwhile adjust their own mechanical properties to maintain stability. The mechanical force is transferred from cell surface or cytoplasm to the nucleus depending on the complete cytoskeletal system. This cytoskeletal system consists of cytoplasmic skeleton and nuclear skeleton, and these two parts are connected mechanically by the LINC complex(linker of nucleoskeleton and cytoskeleton complex), which plays an important role in cellular mechanotransduction. This review discusses the basic structure of mechanical transmission part in LINC complex and the changes in the nuclear morphology, the location of transcription factor, and the spatial conformation of chromatin induced by mechanotransduction, so as to lay a foundation for further exploring the role of LINC complex in cell mechanotransduction and gene expression.
As mechanoreceptors, cells can sense and transmit mechanical forces exerted on their surfaces, meanwhile adjust their own mechanical properties to maintain stability. The mechanical force is transferred from cell surface or cytoplasm to the nucleus depending on the complete cytoskeletal system. This cytoskeletal system consists of cytoplasmic skeleton and nuclear skeleton, and these two parts are connected mechanically by the LINC complex(linker of nucleoskeleton and cytoskeleton complex), which plays an important role in cellular mechanotransduction. This review discusses the basic structure of mechanical transmission part in LINC complex and the changes in the nuclear morphology, the location of transcription factor, and the spatial conformation of chromatin induced by mechanotransduction, so as to lay a foundation for further exploring the role of LINC complex in cell mechanotransduction and gene expression.
引文
[1] VOGEL V,SHEETZ MP.Local force and geometry sensing regulate cell functions [J].Nat Rev Mol Cell Biol,2006,7(4):265-275.
[2] CRISP M,LIU Q,ROUX KJ,et al.Coupling of the nucleus and cytoplasm role of the LINC complex [J].J Cell Biol,2006,172(1):41-53.
[3] HAQUE F,LLOYD D,SMALLWOOD DT,et al.SUN1 Interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton [J].Mol Cell Biol,2006,26(10):3738-51.
[4] PADMAKUMAR VC,LIBOTTE T,LU W,et al.The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope [J].J Cell Sci,2005,118(15):3419-3430.
[5] APEL ED,LEWIS RM,GRADY RM,et al.Syne-1,a dystrophin- and klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction [J].J Biol Chem,2000,275(41):31986-31995.
[6] MISLOW JM,KIM MS,DAVIS DB,et al.Myne-1,a spectrin repeat transmembrane protein of the myocyte inner nuclear membrane,interacts with lamin A/C [J].J Cell Sci,2002,115(1):61-70.
[7] ZHANG Q,SKEPPER J N,YANG F,et al.Nesprins:A novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues [J].J Cell Sci,2001,114(24):4485-4498.
[8] WILHELMSEN K,LITJENS SHM,KUIKMAN I,et al.Nesprin-3,a novel outer nuclear membrane protein,associates with the cytoskeletal linker protein plectin [J].J Cell Biol,2005,171(5):799-810.
[9] ROUX KJ,CRISP M,LIU Q,et al.Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization [J].Proc Natl Acad Sci USA,2009,106(7):2194-2199.
[10] HORN HF,KIM DI,WRIGHT GD,et al.A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton [J].J Cell Biol,2013,202(7):1023-1039.
[11] MORIMOTO A,SHIBUYA H,ZHU X,et al.A conserved KASH domain protein associates with telomeres,SUN1,and dynactin during mammalian meiosis [J].J Cell Biol,2012,198(2):165-172.
[12] STARR DA,FRIDOLFSSON HN.Interactions between nuclei and the cytoskeleton are mediated by SUN-KASH nuclear-envelope bridges [J].Annu Rev Cell Dev Biol,2010,26(1):421-444.
[13] GOB E,SCHMITT J,BENAVENTE R,et al.Mammalian sperm head formation involves different polarization of two novel LINC complexes [J].PLOS One,2010,5(8):e12072.
[14] FROHNERT C,SCHWEIZER S,HOYERFENDER S.SPAG4L/SPAG4L-2 are testis-specific SUN domain proteins restricted to the apical nuclear envelope of round spermatids facing the acrosome [J].Mol Hum Reprod,2011,17(4):207-218.
[15] STARR D,FRIDOLFSSON H.Interactions between nuclei and the cytoskeleton are mediated by SUN-KASH nuclear-envelope bridges [J].Annu Rev Cell Dev Biol,2010,26:421-44.
[16] WANG WJ,SHI ZB,JIAO S,et al.Structural insights into SUN-KASH complexes across the nuclear envelope [J].Cell Res,2012,22(10):1440-1452.
[17] STARR D,HAN M.Role of ANC-1 in tethering nuclei to the actin cytoskeleton [J].Science,2002,298(5592):406-409.
[18] LOMBARDI ML,JAALOUK DE,SHANAHAN CM,et al.The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton [J].J Biol Chem,2011,286(30):26743-26753.
[19] KETEMA M,WILHELMSEN K,KUIKMAN I,et al.Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin [J].J Cell Sci,2007,120(19):3384-3394.
[20] WORMAN HJ,GUNDERSEN GG.Here come the SUNs:A nucleocytoskeletal missing link [J].Trends Cell Biol,2006,16(2):67-69.
[21] ZASTROW MS,FLAHERTY DB,BENIAN GM,et al.Nuclear titin interacts with A- and B-type lamins in vitro and in vivo [J].J Cell Sci,2006,119(2):239-249.
[22] GRANZIER H,LABEIT S.The giant protein titin:A major player in myocardial mechanics,signaling,and disease [J].Circ Res,2004,94(3):284-295.
[23] HAQUE F,MAZZEO D,PATEL JT,et al.Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes [J].J Biol Chem,2010,285(5):3487-3498.
[24] MISLOW JM,HOLASKA JM,KIM MS,et al.Nesprin-1α self-associates and binds directly to emerin and lamin A in vitro [J].FEBS Lett,2002,525(1):135-140.
[25] HOLASKA JM,KOWALSKI AK,WILSON KL.Emerin caps the pointed end of actin filaments:Evidence for an actin cortical network at the nuclear inner membrane [J].PLoS Biol,2004,2(9):E231.
[26] LATTANZI G,CENNI V,MARMIROLI S,et al.Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts [J].Biochem Biophys Res Commun,2003,303(3):764-770.
[27] PEDERSON T.As functional nuclear actin comes into view,is it globular,filamentous,or both?[J].J Cell Biol,2008,180(6):1061-1064.
[28] VREUGDE S,FERRAI C,MILUZIO A,et al.Nuclear myosin VI enhances RNA polymerase II-dependent transcription [J].Mol Cell,2006,23(5):749-755.
[29] YE J,ZHAO J,HOFFMANNROHRER U,et al.Nuclear myosin I acts in concert with polymeric actin to drive RNA polymerase I transcription [J].Genes Dev,2008,22(3):322-330.
[30] PAJEROWSKI J,DAHL K,ZHONG F,et al.Physical plasticity of the nucleus in stem cell differentiation [J].Proc Natl Acad Sci USA,2007,104(40):15619-15624.
[31] JAIN N,IYER K,KUMAR A,et al.Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility [J].Proc Natl Acad Sci USA,2013,110(28):11349-11354.
[32] LI Q,KUMAR A,MAKHIJA E,et al.The regulation of dynamic mechanical coupling between actin cytoskeleton and nucleus by matrix geometry [J].Biomaterials,2014,35(3):961-969.
[33] CHO S,IRIANTO J,DISCHER D.Mechanosensing by the nucleus:From pathways to scaling relationships [J].J Cell Biol,2017,216(2):305-315.
[34] KIM D,WIRTZ D.Cytoskeletal tension induces the polarized architecture of the nucleus [J].Biomaterials,2015,48:161-72.
[35] BUXBOIM A,SWIFT J,IRIANTO J,et al.Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin [J].Curr Biol,2014,24(16):1909-1917.
[36] LAMMERDING J,FONG LG,JI JY,et al.Lamins A and C but not lamin B1 regulate nuclear mechanics [J].J Biol Chem,2006,281(35):25768-25780.
[37] LAMMERDING J,SCHULZE PC,TAKAHASHI T,et al.Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction [J].J Clin Invest,2004,113(3):370-378.
[38] SWIFT J,IVANOVSKA I,BUXBOIM A,et al.Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation [J].Science,2013,341(6149):1240104.
[39] BURKE B,STEWART C.The nuclear lamins:Flexibility in function [J].Nat Rev Mol Cell Biol,2013,14(1):13-24.
[40] PAJEROWSKI JD,DAHL KN,ZHONG FL,et al.Physical plasticity of the nucleus in stem cell differentiation [J].Proc Natl Acad Sci USA,2007,104(40):15619-15624.
[41] UHLER C,SHIVASHANKAR GV.Regulation of genome organization and gene expression by nuclear mechanotransduction [J].Nat Rev Mol Cell Biol,2017,18(12):717-727.
[42] GOETZE S,MATEOS-LANGERAK J,GIERMAN HJ,et al.The three-dimensional structure of human interphase chromosomes is related to the transcriptome map [J].Mol Cell Biol,2007,27(12):4475-4487.
[43] IYER KV,MAHARANA S,GUPTA S,et al.Modeling and experimental methods to probe the link between global transcription and spatial organization of chromosomes [J].Plos One,2012,7(10):e46628.
[44] COOK PR.A model for all genomes:The role of transcription factories [J].J Mol Biol,2010,395(1):1-10.
[45] MAHARANA S,IYER K,JAIN N,et al.Chromosome intermingling-the physical basis of chromosome organization in differentiated cells [J].Nucleic Acids Res,2016,44(11):5148-5160.
[46] WANG Y,NAGARAJAN M,UHLER C,et al.Orientation and repositioning of chromosomes correlate with cell geometry-dependent gene expression [J].Mol Biol Cell,2017,28(14):1997-2009.
[47] WANG Y,BOTVINICK E,ZHAO Y,et al.Visualizing the mechanical activation of Src [J].Nature,2005,434(7036):1040-1045.
[48] VARTIAINEN M,GUETTLER S,LARIJANI B,et al.Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL [J].Science,2007,316(5832):1749-1752.
[49] DUPONT S,MORSUT L,ARAGONA M,et al.Role of YAP/TAZ in mechanotransduction [J].Nature,2011,474(7350):179-183.
[50] TOTARO A,CASTELLAN M,BATTILANA G,et al.YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate [J].Nat Commun,2017,8:15206.
[51] LE H,GHATAK S,YEUNG C,et al.Mechanical regulation of transcription controls polycomb-mediated gene silencing during lineage commitment [J].Nat Cell Biol,2016,18(8):864-875.
[52] SPEIGHT P,KOFLER M,SZASZI K,et al.Context-dependent switch in chemo/mechanotransduction via multilevel crosstalk among cytoskeleton-regulated MRTF and TAZ and TGFβ-regulated Smad3 [J].Nat Commun,2016,7:11642.
[53] QI Y,YAO Q,HUANG K,et al.Nuclear envelope proteins modulate proliferation of vascular smooth muscle cells during cyclic stretch application [J].Proc Natl Acad Sci USA,2016,113(19):5293-5298.
[54] NAKAZAWA N,SATHE A,SHIVASHANKAR G,et al.Matrix mechanics controls FHL2 movement to the nucleus to activate p21 expression [J].Proc Natl Acad Sci USA,2016,113(44):E6813-E6822.
[55] KAUNAS R,NGUYEN P,USAMI S,et al.Cooperative effects of Rho and mechanical stretch on stress fiber organization [J].Proc Natl Acad Sci USA,2005,102(44):15895-15900.
[56] MITRA A,VENKATACHALAPATHY S,RATNA P,et al.Cell geometry dictates TNFα-induced genome response [J].Proc Natl Acad Sci USA,2017,114(20):E3882-E3891.
[2] CRISP M,LIU Q,ROUX KJ,et al.Coupling of the nucleus and cytoplasm role of the LINC complex [J].J Cell Biol,2006,172(1):41-53.
[3] HAQUE F,LLOYD D,SMALLWOOD DT,et al.SUN1 Interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton [J].Mol Cell Biol,2006,26(10):3738-51.
[4] PADMAKUMAR VC,LIBOTTE T,LU W,et al.The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope [J].J Cell Sci,2005,118(15):3419-3430.
[5] APEL ED,LEWIS RM,GRADY RM,et al.Syne-1,a dystrophin- and klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction [J].J Biol Chem,2000,275(41):31986-31995.
[6] MISLOW JM,KIM MS,DAVIS DB,et al.Myne-1,a spectrin repeat transmembrane protein of the myocyte inner nuclear membrane,interacts with lamin A/C [J].J Cell Sci,2002,115(1):61-70.
[7] ZHANG Q,SKEPPER J N,YANG F,et al.Nesprins:A novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues [J].J Cell Sci,2001,114(24):4485-4498.
[8] WILHELMSEN K,LITJENS SHM,KUIKMAN I,et al.Nesprin-3,a novel outer nuclear membrane protein,associates with the cytoskeletal linker protein plectin [J].J Cell Biol,2005,171(5):799-810.
[9] ROUX KJ,CRISP M,LIU Q,et al.Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization [J].Proc Natl Acad Sci USA,2009,106(7):2194-2199.
[10] HORN HF,KIM DI,WRIGHT GD,et al.A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton [J].J Cell Biol,2013,202(7):1023-1039.
[11] MORIMOTO A,SHIBUYA H,ZHU X,et al.A conserved KASH domain protein associates with telomeres,SUN1,and dynactin during mammalian meiosis [J].J Cell Biol,2012,198(2):165-172.
[12] STARR DA,FRIDOLFSSON HN.Interactions between nuclei and the cytoskeleton are mediated by SUN-KASH nuclear-envelope bridges [J].Annu Rev Cell Dev Biol,2010,26(1):421-444.
[13] GOB E,SCHMITT J,BENAVENTE R,et al.Mammalian sperm head formation involves different polarization of two novel LINC complexes [J].PLOS One,2010,5(8):e12072.
[14] FROHNERT C,SCHWEIZER S,HOYERFENDER S.SPAG4L/SPAG4L-2 are testis-specific SUN domain proteins restricted to the apical nuclear envelope of round spermatids facing the acrosome [J].Mol Hum Reprod,2011,17(4):207-218.
[15] STARR D,FRIDOLFSSON H.Interactions between nuclei and the cytoskeleton are mediated by SUN-KASH nuclear-envelope bridges [J].Annu Rev Cell Dev Biol,2010,26:421-44.
[16] WANG WJ,SHI ZB,JIAO S,et al.Structural insights into SUN-KASH complexes across the nuclear envelope [J].Cell Res,2012,22(10):1440-1452.
[17] STARR D,HAN M.Role of ANC-1 in tethering nuclei to the actin cytoskeleton [J].Science,2002,298(5592):406-409.
[18] LOMBARDI ML,JAALOUK DE,SHANAHAN CM,et al.The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton [J].J Biol Chem,2011,286(30):26743-26753.
[19] KETEMA M,WILHELMSEN K,KUIKMAN I,et al.Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin [J].J Cell Sci,2007,120(19):3384-3394.
[20] WORMAN HJ,GUNDERSEN GG.Here come the SUNs:A nucleocytoskeletal missing link [J].Trends Cell Biol,2006,16(2):67-69.
[21] ZASTROW MS,FLAHERTY DB,BENIAN GM,et al.Nuclear titin interacts with A- and B-type lamins in vitro and in vivo [J].J Cell Sci,2006,119(2):239-249.
[22] GRANZIER H,LABEIT S.The giant protein titin:A major player in myocardial mechanics,signaling,and disease [J].Circ Res,2004,94(3):284-295.
[23] HAQUE F,MAZZEO D,PATEL JT,et al.Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes [J].J Biol Chem,2010,285(5):3487-3498.
[24] MISLOW JM,HOLASKA JM,KIM MS,et al.Nesprin-1α self-associates and binds directly to emerin and lamin A in vitro [J].FEBS Lett,2002,525(1):135-140.
[25] HOLASKA JM,KOWALSKI AK,WILSON KL.Emerin caps the pointed end of actin filaments:Evidence for an actin cortical network at the nuclear inner membrane [J].PLoS Biol,2004,2(9):E231.
[26] LATTANZI G,CENNI V,MARMIROLI S,et al.Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts [J].Biochem Biophys Res Commun,2003,303(3):764-770.
[27] PEDERSON T.As functional nuclear actin comes into view,is it globular,filamentous,or both?[J].J Cell Biol,2008,180(6):1061-1064.
[28] VREUGDE S,FERRAI C,MILUZIO A,et al.Nuclear myosin VI enhances RNA polymerase II-dependent transcription [J].Mol Cell,2006,23(5):749-755.
[29] YE J,ZHAO J,HOFFMANNROHRER U,et al.Nuclear myosin I acts in concert with polymeric actin to drive RNA polymerase I transcription [J].Genes Dev,2008,22(3):322-330.
[30] PAJEROWSKI J,DAHL K,ZHONG F,et al.Physical plasticity of the nucleus in stem cell differentiation [J].Proc Natl Acad Sci USA,2007,104(40):15619-15624.
[31] JAIN N,IYER K,KUMAR A,et al.Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility [J].Proc Natl Acad Sci USA,2013,110(28):11349-11354.
[32] LI Q,KUMAR A,MAKHIJA E,et al.The regulation of dynamic mechanical coupling between actin cytoskeleton and nucleus by matrix geometry [J].Biomaterials,2014,35(3):961-969.
[33] CHO S,IRIANTO J,DISCHER D.Mechanosensing by the nucleus:From pathways to scaling relationships [J].J Cell Biol,2017,216(2):305-315.
[34] KIM D,WIRTZ D.Cytoskeletal tension induces the polarized architecture of the nucleus [J].Biomaterials,2015,48:161-72.
[35] BUXBOIM A,SWIFT J,IRIANTO J,et al.Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin [J].Curr Biol,2014,24(16):1909-1917.
[36] LAMMERDING J,FONG LG,JI JY,et al.Lamins A and C but not lamin B1 regulate nuclear mechanics [J].J Biol Chem,2006,281(35):25768-25780.
[37] LAMMERDING J,SCHULZE PC,TAKAHASHI T,et al.Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction [J].J Clin Invest,2004,113(3):370-378.
[38] SWIFT J,IVANOVSKA I,BUXBOIM A,et al.Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation [J].Science,2013,341(6149):1240104.
[39] BURKE B,STEWART C.The nuclear lamins:Flexibility in function [J].Nat Rev Mol Cell Biol,2013,14(1):13-24.
[40] PAJEROWSKI JD,DAHL KN,ZHONG FL,et al.Physical plasticity of the nucleus in stem cell differentiation [J].Proc Natl Acad Sci USA,2007,104(40):15619-15624.
[41] UHLER C,SHIVASHANKAR GV.Regulation of genome organization and gene expression by nuclear mechanotransduction [J].Nat Rev Mol Cell Biol,2017,18(12):717-727.
[42] GOETZE S,MATEOS-LANGERAK J,GIERMAN HJ,et al.The three-dimensional structure of human interphase chromosomes is related to the transcriptome map [J].Mol Cell Biol,2007,27(12):4475-4487.
[43] IYER KV,MAHARANA S,GUPTA S,et al.Modeling and experimental methods to probe the link between global transcription and spatial organization of chromosomes [J].Plos One,2012,7(10):e46628.
[44] COOK PR.A model for all genomes:The role of transcription factories [J].J Mol Biol,2010,395(1):1-10.
[45] MAHARANA S,IYER K,JAIN N,et al.Chromosome intermingling-the physical basis of chromosome organization in differentiated cells [J].Nucleic Acids Res,2016,44(11):5148-5160.
[46] WANG Y,NAGARAJAN M,UHLER C,et al.Orientation and repositioning of chromosomes correlate with cell geometry-dependent gene expression [J].Mol Biol Cell,2017,28(14):1997-2009.
[47] WANG Y,BOTVINICK E,ZHAO Y,et al.Visualizing the mechanical activation of Src [J].Nature,2005,434(7036):1040-1045.
[48] VARTIAINEN M,GUETTLER S,LARIJANI B,et al.Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL [J].Science,2007,316(5832):1749-1752.
[49] DUPONT S,MORSUT L,ARAGONA M,et al.Role of YAP/TAZ in mechanotransduction [J].Nature,2011,474(7350):179-183.
[50] TOTARO A,CASTELLAN M,BATTILANA G,et al.YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate [J].Nat Commun,2017,8:15206.
[51] LE H,GHATAK S,YEUNG C,et al.Mechanical regulation of transcription controls polycomb-mediated gene silencing during lineage commitment [J].Nat Cell Biol,2016,18(8):864-875.
[52] SPEIGHT P,KOFLER M,SZASZI K,et al.Context-dependent switch in chemo/mechanotransduction via multilevel crosstalk among cytoskeleton-regulated MRTF and TAZ and TGFβ-regulated Smad3 [J].Nat Commun,2016,7:11642.
[53] QI Y,YAO Q,HUANG K,et al.Nuclear envelope proteins modulate proliferation of vascular smooth muscle cells during cyclic stretch application [J].Proc Natl Acad Sci USA,2016,113(19):5293-5298.
[54] NAKAZAWA N,SATHE A,SHIVASHANKAR G,et al.Matrix mechanics controls FHL2 movement to the nucleus to activate p21 expression [J].Proc Natl Acad Sci USA,2016,113(44):E6813-E6822.
[55] KAUNAS R,NGUYEN P,USAMI S,et al.Cooperative effects of Rho and mechanical stretch on stress fiber organization [J].Proc Natl Acad Sci USA,2005,102(44):15895-15900.
[56] MITRA A,VENKATACHALAPATHY S,RATNA P,et al.Cell geometry dictates TNFα-induced genome response [J].Proc Natl Acad Sci USA,2017,114(20):E3882-E3891.