Mechanotransduction in Cellular Physiology: From Cytoskeleton Dynamics to Gene Expression
DOI:
https://doi.org/10.48048/tis.2026.12554Keywords:
Mechanotransduction, Cytoskeleton, Disease, Integrins, Gene expression, Mechanical signalingAbstract
Mechanotransduction is the process through which cells convert mechanical cues from their microenvironment into biochemical signals that regulate gene expression and cellular behavior. This review aims to critically integrate current evidence on how mechanical forces are transmitted from the extracellular matrix through adhesion complexes and cytoskeletal structures to the nucleus, thereby shaping transcriptional regulation. The discussion focuses on the coordinated roles of cytoskeletal dynamics and mechanosensitive signaling pathways, including YAP/TAZ, MRTF-A, and RhoA/ROCK, in controlling cellular proliferation, differentiation, and tissue adaptation. The physiological relevance of these mechanisms is examined in key biological contexts such as stem cell lineage specification, skeletal muscle adaptation to mechanical loading, and endothelial regulation under hemodynamic forces. In parallel, the review addresses how disruptions in mechanotransduction contribute to disease pathogenesis, particularly in cancer, fibrosis, and atherosclerosis, where altered mechanical environments lead to aberrant gene regulatory responses. Finally, this article highlights emerging methodological advances, including three-dimensional culture systems, organ-on-chip platforms, and integrated multi-omics approaches, as essential tools for improving mechanobiological modeling and identifying novel therapeutic targets related to mechanically driven cellular dysfunction.
HIGHLIGHTS
- Cytoskeletal force routing through LINC alters chromatin and YAP/TAZ-MRTF pathways.
- The stiffness of the extracellular matrix influences stem cell differentiation and regulates tissue adaptability.
- FAK/Src and RhoA/ROCK combine adhesion signals with contractility.
- Dysregulation of mechanotransduction promotes cancer, fibrosis, and atherogenesis.
- AFM, TFM, 3D organ-on-chip technology, and multi-omics facilitate quantitative mapping.
GRAPHICAL ABSTRACT
Downloads
References
P Elblová, M Lunova, A Dejneka, M Jirsa and O Lunov. Impact of mechanical cues on key cell functions and cell-nanoparticle interactions. Discover Nano 2024; 19(1), 106.
Y Zeng, X Cui, H Li, Y Wang, M Cheng and X Zhang. Extracellular vesicles originating from the mechanical microenvironment in the pathogenesis and applications for cardiovascular diseases. Regenerative Therapy 2024; 26(1), 1069-1977.
P Nitti, A Narayanan, R Pellegrino, S Villani, M Madaghiele and C Demitri. Cell-Tissue Interaction: The biomimetic approach to design tissue engineered biomaterials. Bioengineering (Basel) 2023; 10(10), 1122.
J Su, Y Song, Z Zhu, X Huang, J Fan, J Qiao and F Mao. Cell-cell communication: New insights and clinical implications. Signal Transduction and Targeted Therapy 2024; 9(1), 196.
X Di, X Gao, L Peng, J Ai, X Jin, S Qi, H Li, K Wang and D Luo. Cellular mechanotransduction in health and diseases: From molecular mechanism to therapeutic targets. Signal Transduction and Targeted Therapy 2023; 8(1), 282.
I Muhamed, F Chowdhury and V Maruthamuthu. Biophysical tools to study cellular mechanotransduction. Bioengineering 2017; 4(1), 12.
C Cavallini, E Olivi, R Tassinari and C Ventura. Mechanotransduction, cellular biophotonic activity, and signaling patterns for tissue regeneration. Journal of Biological Chemistry 2024; 300(11), 107847.
A Rojas, S Dahlen, F Zhang and S Liu. The cytoskeletal structure in cardiomyocyte maturation and proliferation. Cells 2025; 14(19), 1494.
J Na, Z Yang, Q Shi, C Li, Y Liu, Y Song, X Li, L Zheng and Y Fan. Extracellular matrix stiffness as an energy metabolism regulator drives osteogenic differentiation in mesenchymal stem cells. Bioactive Materials 2024; 35(1), 549-563.
Q Zheng, Y Zou, P Teng, Z Chen, Y Wu, X Dai, X Li, Z Hu, S Wu, Y Xu, W Zou, H Song and L Ma. Mechanosensitive channel PIEZO1 senses shear force to induce KLF2/4 expression via CaMKII/MEKK3/ERK5 axis in endothelial cells. Cells 2022; 11(14), 2191.
Y Wang, J Meng, J Zhang, L Tian, W Wei, X Tang, Q Zhang, D Ding, X Wang, Z Guo and Y He. Cell biomechanics on muscle atrophy: From intricate mechanisms to therapeutic frontiers. Annals of Medicine 2025; 57(1), 2540598.
R Cao, H Tian, Y Tian and X Fu. A Hierarchical Mechanotransduction System: From Macro to Micro. Advanced Science (Weinh) 2024; 11(11), e2302327.
R Li and W Huang. Yes-associated protein and transcriptional coactivator with PDZ-binding motif in cardiovascular diseases. International Journal of Molecular Sciences 2023; 24(2), 1666.
M Liaghat, S Ferdousmakan, SH Mortazavi, S Yahyazadeh, A Irani, S Banihashemi, FSS Asl, A Akbari, F Farzam, F Aziziyan, M Bakhtiyari, MJ Arghavani, H Zalpoor and M Nabi-Afjadi. The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors. Cell Communication and Signaling 2024; 22(1), 575.
S Jebari-Benslaiman, U Galicia-García, A Larrea-Sebal, JR Olaetxea, I Alloza, K Vandenbroeck, A Benito-Vicente and C Martín. Pathophysiology of atherosclerosis. International Journal of Molecular Sciences 2022; 23(6), 3346.
F Martino, AR Perestrelo, V Vinarský, S Pagliari and G Forte. Cellular Mechanotransduction: From Tension to Function. Frontiers in Physiology 2018; 9(1), 824.
GB Bais and J Giudice. The bidirectional interplay between RNA processing and mechanotransduction. Cell Reports 2025; 44(9), 116175.
IP Uray and K Uray. Mechanotransduction at the plasma Membrane-cytoskeleton Interface. International Journal of Molecular Sciences 2021; 22(21), 11566.
U Mukhopadhyay, T Mandal, M Chakraborty and B Sinha. The Plasma Membrane and Mechanoregulation in Cells. ACS Omega 2024; 9(20), 21780-21797.
P Wang, J Li and Q Wei. Understanding the interplay between cell force and cell adhesion processes. Engineered Regeneration 2023; 4(3), 277-288.
K Katoh. Integrin and Its associated proteins as a mediator for Mechano-signal transduction. Biomolecules 2025; 15(2), 166.
K Katoh. Signal transduction mechanisms of focal adhesions: Src and FAK-Mediated cell response. Frontiers in Bioscience 2024; 29(11), 392.
RM Mège and N Ishiyama. Integration of cadherin adhesion and cytoskeleton at adherens junctions. Cold Spring Harbor Perspectives in Biology 2017; 9(5), a028738.
WH Lin, LM Cooper and PZ Anastasiadis. Cadherins and catenins in cancer: Connecting cancer pathways and tumor microenvironment. Frontiers in Cell and Developmental Biology 2023; 11(1), 1137013.
Z Chen, C Du, S Liu, J Liu, Y Yang, L Dong, W Zhao, W Huang and Y Lei. Progress in biomaterials inspired by the extracellular matrix. Giant 2024; 19(1), 100323.
A Saraswathibhatla, D Indana and O Chaudhuri. Cell-extracellular matrix mechanotransduction in 3D. Nature Reviews Molecular Cell Biology 2023; 24(7), 495-516.
W Xie, X Wei, H Kang, H Jiang, Z Chu, Y Lin, Y Hou and Q Wei. Static and Dynamic: Evolving Biomaterial Mechanical Properties to Control Cellular Mechanotransduction. Advanced Science 2023; 10(9), e2204594.
X Cai, KC Wang and Z Meng. Mechanoregulation of YAP and TAZ in cellular homeostasis and disease progression. Frontiers in Cell and Developmental Biology 2021; 9(1), 673599.
M Zhang and B Zhang. Extracellular matrix stiffness: Mechanisms in tumor progression and therapeutic potential in cancer. Experimental Hematology & Oncology 2025; 14(1), 54.
T Zhao, Y Huang, J Zhu, Y Qin, H Wu, J Yu, Q Zhai, S Li, X Qin, D Wang, T Li and Y Liu. Extracellular matrix signaling cues: Biological functions, diseases, and therapeutic targets. MedComm 2025; 6(8), e70281.
T Hohmann and F Dehghani. The Cytoskeleton-A complex interacting meshwork. Cells 2019; 8(4), 362.
R Sanghvi-Shah and GF Weber. Intermediate filaments at the junction of mechanotransduction, migration, and development. Frontiers in Cell and Developmental Biology 2017; 5(1), 81.
T Svitkina. The actin cytoskeleton and actin-based motility. Cold Spring Harbor Perspectives in Biology 2018; 10(1), a018267.
E Infante and S Etienne-Manneville. Intermediate filaments: Integration of cell mechanical properties during migration. Frontiers in Cell and Developmental Biology 2022; 10(1), 951816.
J Salvador and ML Iruela-Arispe. Nuclear mechanosensation and mechanotransduction in vascular cells. Frontiers in Cell and Developmental Biology 2022; 10(1), 905927.
E Momotyuk, N Ebrahim, K Shakirova and E Dashinimaev. Role of the cytoskeleton in cellular reprogramming: Effects of biophysical and biochemical factors. Frontiers in Molecular Biosciences 2025; 12(1), 1538806.
EK Pillai and K Franze. Mechanics in the nervous system: From development to disease. Neuron 2024; 112(3), 342-361.
EK Paluch, CM Nelson, N Biais, B Fabry, J Moeller, BL Pruitt, C Wollnik, G Kudryasheva, F Rehfeldt and W Federle. Mechanotransduction: Use the force(s). BMC Biology 2015; 13(1), 47.
D Mohammed, I Hamid, B Vanhollebeke and M Martin. Microtubules and mechanosensing: Key players in endothelial responses to mechanical stimuli. Cellular and Molecular Life Sciences 2025; 82(1), 317.
K Legerstee and AB Houtsmuller. A layered view on focal adhesions. Biology 2021; 10(11), 1189.
H Wang, R Said, C Nguyen-Vigouroux, V Henriot, P Gebhardt, J Pernier, R Grosse and CL Clainche. Talin and vinculin combine their activities to trigger actin assembly. Nature Communications 2024; 15(1), 9497.
T Izard and DT Brown. Mechanisms and functions of vinculin interactions with phospholipids at cell adhesion sites. Journal of Biological Chemistry 2016; 291(6), 2548-2555.
P Ridone, M Vassalli and B Martinac. Piezo1 mechanosensitive channels: What are they and why are they important. Biophysical Reviews 2019; 11(5), 795-805.
G Yuan, Z Xiong, X Ke, G Wang, X Liu and Z Li. Exploring the multifactorial regulation of PIEZO1 in chondrocytes: Mechanisms and implications. International Journal of Medical Sciences 2025; 22(13), 3393-3411.
Q Zhang, X Han, J Chen, X Xie, J Xu, Y Zhao, J Shen, L Hu, P Xu, H Song, L Zhang, B Zhao, YJ Wang and Z Xia. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) mediate cell density-dependent proinflammatory responses. Journal of Biological Chemistry 2018; 293(47), 18071-18085.
Y Wei, VLZ Hui, Y Chen, R Han, X Han and Y Guo. YAP/TAZ: Molecular pathway and disease therapy. MedComm 2023; 4(4), e340.
Y Li, J Wang and W Zhong. Regulation and mechanism of YAP/TAZ in the mechanical microenvironment of stem cells (review). Molecular Medicine Reports 2021; 24(1), 506.
M Ozu, L Galizia, JJ Alvear-Arias, M Fernández, A Caviglia, R Zimmermann, F Guastaferri, N Espinoza-Muñoz, M Sutka, L Sigaut, LI Pietrasanta, C González, G Amodeo and JA Garate. Mechanosensitive aquaporins. Biophysical Reviews 2023; 15(4), 497-513.
S Vajda, D Beglov, AE Wakefield, M Egbert and A Whitty. Cryptic binding sites on proteins: Definition, detection, and druggability. Current Opinion in Chemical Biology 2018; 44, 1-8.
Y Wang, M Yao, KB Baker, RE Gough, S Le, BT Goult and J Yan. Force-dependent interactions between talin and full-length vinculin. Journal of the American Chemical Society 2021; 143(36), 14726-14737.
A Buchwalter. Intermediate, but not average: The unusual lives of the nuclear lamin proteins. Current Opinion in Cell Biology 2023; 84(1), 102220.
J Jo, SA Nansa and DH Kim. Molecular regulators of cellular mechanoadaptation at Cell-material interfaces. Frontiers in Bioengineering and Biotechnology 2020; 8(1), 608569.
G Guan, RD Cannon, DE Coates and L Mei. Effect of the Rho-Kinase/ROCK Signaling pathway on cytoskeleton components. Genes 2023; 14(2), 272.
C Braicu, M Buse, C Busuioc, R Drula, D Gulei, L Raduly, A Rusu, A Irimie, AG Atanasov, O Slaby, C Ionescu and I Berindan-Neagoe. A comprehensive review on MAPK: A promising therapeutic target in cancer. Cancers 2019; 11(10), 1618.
ST Eblen. Extracellular-regulated kinases: Signaling from Ras to ERK substrates to control biological outcomes. Advances in Cancer Research 2018; 138(1), 99-142.
T Pungsrinont, J Kallenbach and A Baniahmad. Role of PI3K-AKT-mTOR pathway as a pro-survival signaling and resistance-mediating mechanism to therapy of prostate cancer. International Journal of Molecular Sciences 2021; 22(20), 11088.
I Tortorella, C Argentati, C Emiliani, F Morena and S Martino. Biochemical pathways of cellular mechanosensing/mechanotransduction and their role in neurodegenerative diseases pathogenesis. Cells 2022; 11(19), 3093.
DA Fletcher and RD Mullins. Cell mechanics and the cytoskeleton. Nature 2010; 463(7280), 485-492.
G Yuan, H Gao and T Yang. Exploring the role of the plant actin cytoskeleton: From signaling to cellular functions. International Journal of Molecular Sciences 2023; 24(20), 15480.
LS Mosby, N Hundt, G Young, A Fineberg, M Polin, S Mayor, P Kukura and DV Köster. Myosin II filament dynamics in actin networks revealed with interferometric scattering microscopy. Biophysical Journal 2020; 118(8), 1946-1957.
H Katsuta, M Sokabe and H Hirata. From stress fiber to focal adhesion: A role of actin crosslinkers in force transmission. Frontiers in Cell and Developmental Biology 2024; 12(1), 1444827.
K Bhadriraju, M Yang, SA Ruiz, D Pirone, J Tan and CS Chen. Activation of ROCK by RhoA is regulated by cell adhesion, shape, and cytoskeletal tension. Experimental Cell Research 2007; 313(16), 3616-3623.
K Okura, T Matsumoto, A Narita and H Tatsumi. Mechanical stress decreases the amplitude of twisting and bending fluctuations of actin filaments. Journal of Molecular Biology 2023; 435(22), 168295.
BV Fearing, L Jing, MN Barcellona, SE Witte, JM Buchowski, LP Zebala, MP Kelly, S Luhmann, MC Gupta, A Pathak and LA Setton. Mechanosensitive transcriptional coactivators MRTF-A and YAP/TAZ regulate nucleus pulposus cell phenotype through cell shape. The FASEB Journal 2019; 33(12), 14022-14035.
X Sun and GM Alushin. Cellular force-sensing through actin filaments. The FEBS Journal 2023; 290(10), 2576-2589.
A Pacheco and G Gallo. Actin filament-microtubule interactions in axon initiation and branching. Brain Research Bulletin 2016; 126, 300-310.
M Ezzo and S Etienne-Manneville. Microtubule-targeting agents: Advances in tubulin binding and small molecule therapy for gliomas and neurodegenerative diseases. International Journal of Molecular Sciences 2025; 26(15), 7652.
HV Goodson and EM Jonasson. Microtubules and microtubule-associated proteins. Cold Spring Harbor Perspectives in Biology 2018; 10(6), a022608.
J Singh, P Sanghavi and R Mallik. Microtubule motor driven interactions of lipid droplets: Specificities and opportunities. Frontiers in Cell and Developmental Biology 2022; 10(1), 893375.
A Rape, WH Guo and YL Wang. Microtubule depolymerization induces traction force increase through two distinct pathways. Journal of Cell Science 2011; 124, 4233-4240.
CS Tong, M Su, H Sun, XL Chua, D Xiong, S Guo, R Raj, NWP Ong, AG Lee, Y Miao and M Wu. Collective dynamics of actin and microtubule and its crosstalk mediated by FHDC1. Frontiers in Cell and Developmental Biology 2024; 11(1), 1261117.
B MacTaggart and A Kashina. Posttranslational modifications of the cytoskeleton. Cytoskeleton 2021; 78(4), 142-173.
H Yamaguchi and J Condeelis. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochimica et Biophysica Acta 2007; 1773(5), 642-652.
JP Conboy, II Petitjean, AVD Net and GH Koenderink. How cytoskeletal crosstalk makes cells move: Bridging cell-free and cell studies. Biophysical Reviews 2024; 5(2), 021307.
CT Mierke. Extracellular matrix cues regulate mechanosensing and mechanotransduction of cancer cells. Cells 2024; 13(1), 96.
K Katoh. Effects of mechanical stress on endothelial cells in situ and In Vitro. International Journal of Molecular Sciences 2023; 24(22), 16518.
SC Carim, A Kechad and GRX Hickson. Animal cell cytokinesis: The Rho-dependent actomyosin-anilloseptin contractile ring as a membrane microdomain gathering, compressing, and sorting machine. Frontiers in Cell and Developmental Biology 2020; 8(1), 575226.
F Prieto-Ruiz, E Gómez-Gil, R Martín-García, AJ Pérez-Díaz, J Vicente-Soler, A Franco, T Soto, P Pérez, M Madrid and J Cansado. Myosin II regulatory light chain phosphorylation and formin availability modulate cytokinesis upon changes in carbohydrate metabolism. Elife 2023; 12(1), e83285.
M Hirano and K Hirano. Critical role of Rho proteins in myosin light chain di-phosphorylation during early phase of endothelial barrier disruption. The Journal of Physiological Sciences 2022; 72(1), 32.
OM Rossier, N Gauthier, N Biais, W Vonnegut, MA Fardin, P Avigan, ER Heller, A Mathur, S Ghassemi, MS Koeckert, JC Hone and MP Sheetz. Force generated by actomyosin contraction builds bridges between adhesive contacts. The EMBO Journal 2010; 29(6), 1055-1068.
KH Vining and DJ Mooney. Mechanical forces direct stem cell behaviour in development and regeneration. Nature Reviews Molecular Cell Biology 2017; 18(12), 728-742.
T Bouzid, E Kim, BD Riehl, AM Esfahani, J Rosenbohm, R Yang, B Duan and JY Lim. The LINC complex, mechanotransduction, and mesenchymal stem cell function and fate. Journal of Biological Engineering 2019; 13(1), 68.
X Tan, Y Yan, B Song, S Zhu, Q Mei and K Wu. Focal adhesion kinase: From biological functions to therapeutic strategies. Experimental Hematology & Oncology 2023; 12(1), 83.
EK Duperret, A Dahal and TW Ridky. Focal-adhesion-independent integrin-αv regulation of FAK and c-Myc is necessary for 3D skin formation and tumor invasion. Journal of Cell Science 2015; 128(21), 3997-4013.
K Katoh. FAK-Dependent Cell Motility and Cell Elongation. Cells 2020; 9(1), 192.
N Mosaddeghzadeh and MR Ahmadian. The RHO Family GTPases: Mechanisms of Regulation and Signaling. Cells 2021; 10(7), 1831.
J Hicks-Berthet and X Varelas. Integrin-FAK-CDC42-PP1A signaling gnaws at YAP/TAZ activity to control incisor stem cells. Bioessays 2017; 39(10), 1700116.
JZ Kechagia, J Ivaska and P Roca-Cusachs. Integrins as biomechanical sensors of the microenvironment. Nature Reviews Molecular Cell Biology 2019; 20(8), 457-473.
R Kolasangiani, TC Bidone and MA Schwartz. Integrin conformational dynamics and mechanotransduction. Cells 2022; 11(22), 3584.
P Atherton, B Stutchbury, D Jethwa and C Ballestrem. Mechanosensitive components of integrin adhesions: Role of vinculin. Experimental Cell Research 2016; 343(1), 21-27.
C Oses, MCD Rossi, L Bruno, P Verneri, MC Diaz, B Benítez, A Guberman and V Levi. From the membrane to the nucleus: Mechanical signals and transcription regulation. Biophysical Reviews 2023; 15(4), 671-683.
G Uzer, CT Rubin and J Rubin. Cell mechanosensitivity is enabled by the LINC nuclear complex. Current Molecular Biology Reports 2016; 2(1), 36-47.
RM McGillivary, DA Starr and GWG Luxton. Building and breaking mechanical bridges between the nucleus and cytoskeleton: Regulation of LINC complex assembly and disassembly. Current Opinion in Cell Biology 2023; 85(1), 102260.
M Hieda. Signal transduction across the nuclear envelope: Role of the LINC complex in bidirectional signaling. Cells 2019; 8(2), 124.
BRM Meqbel, M Gomes, A Omer, IE Gallouzi and HF Horn. LINCing senescence and nuclear envelope changes. Cells 2022; 11(11), 1787.
DH Kim and D Wirtz. Cytoskeletal tension induces the polarized architecture of the nucleus. Biomaterials 2015; 48(1), 161-172.
YA Miroshnikova and SA Wickström. Mechanical forces in nuclear organization. Cold Spring Harbor Perspectives in Biology 2022; 14(1), a039685.
TP Lele, RB Dickinson and GG Gundersen. Mechanical principles of nuclear shaping and positioning. Journal of Cell Biology 2018; 217(10), 3330-3342.
M Kloc and J Wosik. mechanical forces, nucleus, chromosomes, and chromatin. Biomolecules 2025; 15(3), 354.
N Dubik and S Mai. Lamin A/C: Function in normal and tumor cells. Cancers 2020; 12(12), 3688.
N Alcorta-Sevillano, I Macías, CI Rodríguez and A Infante. Crucial role of lamin A/C in the migration and differentiation of MSCs in bone. Cells 2020; 9(6), 1330.
Y Song, J Soto and S Li. Mechanical regulation of histone modifications and cell plasticity. Current Opinion in Solid State and Materials Science 2020; 24(6), 100872.
S Ibragić, S Dahija and E Karalija. The good, the bad, and the epigenetic: Stress-induced metabolite regulation and transgenerational effects. Epigenomes 2025; 9(2), 10.
R Melchionna, P Trono, A Tocci and P Nisticò. Actin cytoskeleton and regulation of TGFβ signaling: Exploring their links. Biomolecules 2021; 11(2), 336.
W Hong and KL Guan. The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway. Seminars in Cell and Developmental Biology 2012; 23(7), 785-793.
NA Perez-Gonzalez, ND Rochman, K Yao, J Tao, MT Le, S Flanary, L Sablich, B Toler, E Crentsil, F Takaesu, B Lambrus, J Huang, V Fu, P Chengappa, TM Jones, AJ Holland, S An, D Wirtz, RJ Petrie, KL Guan and SX Sun. YAP and TAZ regulate cell volume. Journal of Cell Biology 2019; 218(10), 3472-3488.
S Paul, S Xie, X Yao and A Dey. Transcriptional regulation of the hippo pathway: Current understanding and insights from single-cell technologies. Cells 2022; 11(14), 2225.
Á Ortega, I Vera, MP Diaz, C Navarro, M Rojas, W Torres, H Parra, J Salazar, JB De Sanctis and V Bermúdez. The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises. International Journal of Molecular Sciences 2021; 23(1), 430.
E Sidorenko and MK Vartiainen. Nucleoskeletal regulation of transcription: Actin on MRTF. Experimental Biology and Medicine 2019; 244(15), 1372-1381.
BR Frieden and RA Gatenby. Signal transmission through elements of the cytoskeleton form an optimized information network in eukaryotic cells. Scientific Reports 2019; 9(1), 6110.
AA Khilan, NA Al-Maslamani and HF Horn. Cell stretchers and the LINC complex in mechanotransduction. Archives of Biochemistry and Biophysics 2021; 702(1), 108829.
PA Janmey, RG Wells, RK Assoian and CA McCulloch. From tissue mechanics to transcription factors. Differentiation 2013; 86(3), 112-120.
K Wagh, M Ishikawa, DA Garcia, DA Stavreva, A Upadhyaya and GL Hager. Mechanical regulation of transcription: Recent advances. Trends in Cell Biology 2021; 31(6), 457-472.
KN Dahl, AJ Ribeiro and J Lammerding. Nuclear shape, mechanics, and mechanotransduction. Circulation Research 2008; 102(11), 1307-1318.
RB Mokhtari, N Ashayeri, L Baghaie, M Sambi, K Satari, N Baluch, DA Bosykh, MR Szewczuk and S Chakraborty. The hippo pathway effectors YAP/TAZ-TEAD oncoproteins as emerging therapeutic targets in the tumor microenvironment. Cancers 2023; 15(13), 3468.
Z Zhang, P He, L Yang, J Gong, R Qin and M Wang. Posttranslational modifications of YAP/TAZ: Molecular mechanisms and therapeutic opportunities. Cellular and Molecular Biology Letters 2025; 30(1), 83.
A Hooglugt, MMVD Stoel, RA Boon and S Huveneers. Endothelial YAP/TAZ Signaling in Angiogenesis and tumor vasculature. Frontiers in Oncology 2021; 10(1), 612802.
JX Shen, L Zhang, HH Liu, ZY Zhang, N Zhao, JB Zhou, LL Qian and RX Wang. The mechanical role of YAP/TAZ in the development of diabetic cardiomyopathy. Current Issues in Molecular Biology 2025; 47(5), 297.
A Lopez-Hernandez, S Sberna and S Campaner. Emerging principles in the transcriptional control by YAP and TAZ. Cancers 2021; 13(16), 4242.
F Reed, ST Larsuel, MY Mayday, V Scanlon and DS Krause. MRTFA: A critical protein in normal and malignant hematopoiesis and beyond. Journal of Biological Chemistry 2021; 296(1), 100543.
EN Olson and A Nordheim. Linking actin dynamics and gene transcription to drive cellular motile functions. Nature Reviews Molecular Cell Biology 2010; 11(5), 353-365.
S Mascharak, JL Guo, M Griffin, CE Berry, DC Wan and MT Longaker. Modelling and targeting mechanical forces in organ fibrosis. Nature Reviews Bioengineering 2024; 2(4), 305-323.
JM Cook-Mills, ME Marchese and H Abdala-Valencia. Vascular cell adhesion molecule-1 expression and signaling during disease: Regulation by reactive oxygen species and antioxidants. Antioxidants and Redox Signaling 2011; 15(6), 1607-1638.
L Hu, W Chen, A Qian and YP Li. Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease. Bone Research 2024; 12(1), 39.
SA Dabravolski, VN Sukhorukov, VA Kalmykov, AV Grechko, NK Shakhpazyan and AN Orekhov. The Role of KLF2 in the regulation of atherosclerosis development and potential Use of KLF2-Targeted Therapy. Biomedicines 2022; 10(2), 254.
K Tatebe, A Zeytun, RM Ribeiro, R Hoffmann, KS Harrod and CV Forst. Response network analysis of differential gene expression in human epithelial lung cells during avian influenza infections. BMC Bioinformatics 2010; 11(1), 170.
B Chaqour and M Goppelt-Struebe. Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins. The FEBS Journal 2006; 273(16), 3639-3649.
B Hu, D Zhou, H Wang, N Hu and W Zhao. Mechanical cues regulate histone modifications and cell behavior. Stem Cells International 2022; 2022(1), 9179111.
E Carley, MC King and S Guo. Integrating mechanical signals into cellular identity. Trends in Cell Biology 2022; 32(8), 669-680.
Z Lichner, M Ding, T Khare, Q Dan, R Benitez, M Praszner, X Song, R Saleeb, B Hinz, Y Pei, K Szászi and A Kapus. Myocardin-related transcription factor mediates epithelial fibrogenesis in polycystic kidney disease. Cells 2024; 13(11), 984.
MD Pankratova, AA Riabinin, EA Butova, AV Selivanovskiy, EI Morgun, SV Ulianov, EA Vorotelyak and EP Kalabusheva. YAP/TAZ signalling controls epidermal keratinocyte fate. International Journal of Molecular Sciences 2024; 25(23), 12903.
H Das, A Kumar, Z Lin, WD Patino, PM Hwang, MW Feinberg, PK Majumder and MK Jain. Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes. Proceedings of the National Academy of Sciences of the United States of America 2006; 103(17), 6653-6658.
A Kindberg, JK Hu and JO Bush. Forced to communicate: Integration of mechanical and biochemical signaling in morphogenesis. Current Opinion in Cell Biology 2020; 66(1), 59-68.
M Lucariello, ML Valicenti, S Giannoni, L Donati, I Armentano, F Morena and S Martino. Mechanobiology in Action: Biomaterials, Devices, and the Cellular Machinery of Force Sensing. Biomolecules 2025; 15(6), 848.
LR Smith, S Cho and DE Discher. Stem cell differentiation is regulated by extracellular matrix mechanics. Physiology 2018; 33(1), 16-25.
S Nellinger and PJ Kluger. How mechanical and physicochemical material characteristics influence adipose-derived stem cell fate. International Journal of Molecular Sciences 2023; 24(4), 3551.
BC Heng, X Zhang, D Aubel, Y Bai, X Li, Y Wei, M Fussenegger and X Deng. Role of YAP/TAZ in cell lineage fate determination and related signaling pathways. Frontiers in Cell and Developmental Biology 2020; 8(1), 735.
JK Virdi and P Pethe. Biomaterials Regulate Mechanosensors YAP/TAZ in Stem Cell Growth and differentiation. Tissue Engineering and Regenerative Medicine 2021; 18(2), 199-215.
S Schiaffino, C Reggiani, T Akimoto and B Blaauw. Molecular mechanisms of skeletal muscle hypertrophy. Journal of Neuromuscular Diseases 2021; 8(2), 169-183.
MA Egerman and DJ Glass. Signaling pathways controlling skeletal muscle mass. Critical Reviews in Biochemistry and Molecular Biology 2014; 49(1), 59-68.
H Cheng, W Zhong, L Wang, Q Zhang, X Ma, Y Wang, S Wang, C He, Q Wei and C Fu. Effects of shear stress on vascular endothelial functions in atherosclerosis and potential therapeutic approaches. Biomedicine and Pharmacotherapy 2023; 158(1), 114198.
N Baeyens, C Bandyopadhyay, BG Coon, S Yun and MA Schwartz. Endothelial fluid shear stress sensing in vascular health and disease. Journal of Clinical Investigation 2016; 126(3), 821-828.
S Chatterjee. Endothelial mechanotransduction, redox signaling and the regulation of vascular inflammatory pathways. Frontiers in Physiology 2018; 9(1), 524.
P Theofilis, M Sagris, E Oikonomou, AS Antonopoulos, G Siasos, C Tsioufis and D Tousoulis. Inflammatory mechanisms contributing to endothelial dysfunction. Biomedicines 2021; 9(7), 781.
A Chalkias. Shear stress and endothelial mechanotransduction in trauma patients with hemorrhagic shock: Hidden coagulopathy pathways and novel therapeutic strategies. International Journal of Molecular Sciences 2023; 24(24), 17522.
HM Han, SY Kim and DH Kim. Mechanotransduction for therapeutic approaches: Cellular aging and rejuvenation. APL Bioengineering 2025; 9(2), 021502.
Y Yokoyama, N Domkam, H Kabir, A Mansour, S Tsukamoto, G Yerima, T Adachi and MRK Mofrad. Emerging mechanomedicines informed by mechanotransduction along the integrin-cytoskeleton-nucleus axis. APL Bioengineering 2025; 9(2), 021503.
E Henke, R Nandigama and S Ergün. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Frontiers in Molecular Biosciences 2020; 6(1), 160.
M Cobbaut, S Karagil, L Bruno, MDCD de la Loza, FE Mackenzie, M Stolinski and A Elbediwy. Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo pathway as a feature of chronic disease. Cells 2020; 9(1), 151.
JT Parsons, AR Horwitz and MA Schwartz. Cell adhesion: Integrating cytoskeletal dynamics and cellular tension. Nature Reviews Molecular Cell Biology 2010; 11(9), 633-643.
MR Zanotelli and CA Reinhart-King. Mechanical forces in tumor angiogenesis. Advances in Experimental Medicine and Biology 2018; 1092(1), 91-112.
BM Lozinski, S Ghorbani and VW Yong. Biology of neurofibrosis with focus on multiple sclerosis. Frontiers in Immunology 2024; 15(1), 1370107.
Y Tai, EL Woods, J Dally, D Kong, R Steadman, R Moseley and AC Midgley. Myofibroblasts: Function, formation, and scope of molecular therapies for skin fibrosis. Biomolecules 2021; 11(8), 1095.
H Liu, M Sun, N Wu, B Liu, Q Liu and X Fan. TGF-β/Smads signaling pathway, Hippo-YAP/TAZ signaling pathway, and VEGF: Their mechanisms and roles in vascular remodeling related diseases. Immunity, Inflammation and Disease 2023; 11(11), e1060.
B Hinz and D Lagares. Evasion of apoptosis by myofibroblasts: A hallmark of fibrotic diseases. Nature Reviews Rheumatology 2020; 16(1), 11-31.
X Wang, Y Shen, M Shang, X Liu and LL Munn. Endothelial mechanobiology in atherosclerosis. Cardiovascular Research 2023; 119(8), 1656-1675.
SA Dabravolski, VN Sukhorukov, VA Kalmykov, AV Grechko, NK Shakhpazyan and AN Orekhov. The role of KLF2 in the regulation of atherosclerosis development and potential Use of KLF2-Targeted therapy. Biomedicines 2022; 10(2), 254.
V Kopych, ADS Da Costa and K Park. Endothelial dysfunction in atherosclerosis: Experimental models and therapeutics. Biomaterials Research 2025; 29(1), 0252.
MJ Herzog, P Müller, K Lechner, M Stiebler, P Arndt, M Kunz, D Ahrens, A Schmeißer, S Schreiber and RC Braun-Dullaeus. Arterial stiffness and vascular aging: Mechanisms, prevention, and therapy. Signal Transduction and Targeted Therapy 2025; 10(1), 282.
DD Rosario-Gilabert, A Valenzuela-Miralles and G Esquiva. Advances in mechanotransduction and sonobiology: Effects of audible acoustic waves and low-vibration stimulations on mammalian cells. Biophysical Reviews 2024; 16(6), 783-812.
W Sun, X Gao, H Lei, W Wang and Y Cao. Biophysical approaches for applying and measuring biological forces. Advanced Science 2022; 9(5), e2105254.
O Padovan-Merhar and A Raj. Using variability in gene expression as a tool for studying gene regulation. Wiley Interdisciplinary Reviews: Systems Biology and Medicine 2013; 5(6), 751-759.
K Haase and AE Pelling. Investigating cell mechanics with atomic force microscopy. Journal of the Royal Society Interface 2015; 12(104), 20140970.
DH Cho, S Aguayo and AX Cartagena-Rivera. Atomic force microscopy-mediated mechanobiological profiling of complex human tissues. Biomaterials 2023; 303(1), 122389.
X Hu and M Bao. Advances in micropatterning technology for mechanotransduction research. Mechanobiology in Medicine 2024; 2(3), 100066.
A Zancla, P Mozetic, M Orsini, G Forte and A Rainer. A primer to traction force microscopy. Journal of Biological Chemistry 2022; 298(5), 101867.
AK Denisin, H Kim, IH Riedel-Kruse and BL Pruitt. Field guide to traction force microscopy. Cellular and Molecular Bioengineering 2024; 17(2), 87-106.
GD Marconi, A Mazzone, YD Rocca, O Trubiani, J Pizzicannella and F Diomede. Three-Dimensional culture system: A new frontier in cancer research, drug discovery, and stem cell-based therapy. Biology 2025; 14(7), 875.
WH Abuwatfa, WG Pitt and GA Husseini. Scaffold-based 3D cell culture models in cancer research. Journal of Biomedical Science 2024; 31(1), 7.
L An, Y Liu and Y Liu. Organ-on-a-Chip applications in microfluidic platforms. Micromachines 2025; 16(2), 201.
AG Monteduro, S Rizzato, G Caragnano, A Trapani, G Giannelli and G Maruccio. Organs-on-chips technologies - A guide from disease models to opportunities for drug development. Biosensors and Bioelectronics 2023; 231(1), 115271.
KR Kukurba and SB Montgomery. RNA sequencing and analysis. Cold Spring Harbor Protocols 2015; 2015(11), 951-969.
H Tekin, S Simmons, B Cummings, L Gao, X Adiconis, CC Hession, A Ghoshal, D Dionne, SR Choudhury, V Yesilyurt, NE Sanjana, X Shi, C Lu, M Heidenreich, JQ Pan, JZ Levin and F Zhang. Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons. Nature Biomedical Engineering 2018; 2(7), 540-554.
DL Jones, GF Hallström, X Jiang, RC Locke, MK Evans, ED Bonnevie, A Srikumar, TP Leahy, MP Nijsure, JD Boerckel, RL Mauck and NA Dyment. Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz. Proceedings of the National Academy of Sciences of the United States of America 2023; 120(22), e2211947120.
BV Fearing, L Jing L, MN Barcellona, SE Witte, JM Buchowski, LP Zebala, MP Kelly, S Luhmann, MC Gupta, A Pathak and LA Setton. Mechanosensitive transcriptional coactivators MRTF-A and YAP/TAZ regulate nucleus pulposus cell phenotype through cell shape. The FASEB Journal 2019; 33(12), 14022-14035.
J Isaacson and M Brotto. Physiology of mechanotransduction: How do muscle and bone “Talk” to one another? Clinical Reviews in Bone and Mineral Metabolism 2014; 12(2), 77-85.
PF Lenne, E Munro, I Heemskerk, A Warmflash, L Bocanegra-Moreno, K Kishi, A Kicheva, Y Long, A Fruleux, A Boudaoud, TE Saunders, P Caldarelli, A Michaut, J Gros, Y Maroudas-Sacks, K Keren, E Hannezo, ZJ Gartner, B Stormo, A Gladfelter, A Rodrigues, A Shyer, N Minc, JL Maître, S Di Talia, B Khamaisi, D Sprinzak and S Tlili. Roadmap for the multiscale coupling of biochemical and mechanical signals during development. Physical Biology 2021; 18(4), 041501.
J Wang, D Lü, D Mao and M Long. Mechanomics: An emerging field between biology and biomechanics. Protein and Cell 2014; 5(7), 518-531.
PHG Sanches, NCD Melo, AM Porcari and LMD Carvalho. Integrating molecular perspectives: Strategies for comprehensive multi-omics integrative data analysis and machine learning applications in transcriptomics, proteomics, and metabolomics. Biology 2024; 13(11), 848.
O Ntousi, M Roumpi, PK Siogkas, D Polyzos, I Kakkos, GK Matsopoulos and DI Fotiadis. Advances in computational modeling of scaffolds for bone tissue engineering: A narrative review of the current approaches and challenges. Biomechanics 2025; 5(4), 76.
R Oria, K Jain and VM Weaver. Exploring the intersection of mechanobiology and artificial intelligence. Npj Biological Physics and Mechanics 2025; 2(1), 9.
L Donati, ML Valicenti, S Giannoni, F Morena and S Martino. Biomaterials mimicking mechanobiology: A Specific design for a specific biological application. International Journal of Molecular Sciences 2024; 25(19), 10386.
W Tiskratok, N Chuinsiri, P Limraksasin, M Kyawsoewin and P Jitprasertwong. Extracellular matrix stiffness: mechanotransduction and mechanobiological response-driven strategies for biomedical applications targeting fibroblast inflammation. Polymers 2025; 17(6), 822.
LE Charelli, JPD Ferreira, CP Naveira-Cotta and TA Balbino. Engineering mechanobiology through organoids-on-chip: A strategy to boost therapeutics. Journal of Tissue Engineering and Regenerative Medicine 2021; 15(11), 883-899.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Walailak University
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
