Role of mechanical properties of T cells in shaping the immune response

Recent studies in immunology highlight the critical role of mechanical factors in shaping the immune response. Mechanoimmunology, being an emerging interdisciplinary field, concerns the influence of mechanical stimuli on immune cell behavior, in particularly, T lymphocytes. Microenvironment stiffness, mechanical interactions with the extracellular matrix, and changes in membrane tension are able to modulate T cell activation, migration, proliferation, and effector functions. An optimal mechanical environment enhances T cell activity, whereas increased stiffness of the microenvironment and alterations in extracellular matrix properties may reduce their functional capacity. Key molecules such as Piezo 1, integrins, and Yes-associated protein serve as central regulators of mechanotransduction in immune cells. The expanding knowledge on their role in immune interactions suggests a high degree of interconnected modulation, resulting into a system of coordinated responses to mechanical stimuli. Mechanomodulation alters the intracellular environment, acting as a determinant of metabolic profile of T cell populations. Moreover, these studies presume that mechanosensitive signaling pathways may regulate intercellular interactions and adaptive immune responses, offering broad opportunities for modifying immune reactions. Understanding the mechanotransduction mechanisms provides new prospects for the development of novel therapeutic strategies. Mechanical signals may be leveraged to enhance the efficacy of CAR-T cells by optimizing their activation, proliferation, and infiltration into tumor tissue, which is particularly important in treating malignant neoplasms, especially solid tumors, where CAR-T cell therapy faces significant limitations. Mechanoimmunological approaches are also being explored in the context of autoimmune disease treatment. It is hypothesized that mechanosensitive pathways may regulate excessive T cell activation, preventing autoimmune processes and pathological hyperactivation of the immune system. Moreover, development of effective methods for preventing graft-versus-host disease and transplant rejection, as well as strategies for treating chronic infections, remains an important goal. The spectrum of potential pharmacological interventions includes the use of activators and inhibitors of Piezo 1, integrins, and Yes-associated protein. Bioengineering approaches are also being actively developed. One promising direction involves the use of nanomotors for ex vivo T cell activation, which may improve the efficacy of cellular immunotherapy in various diseases. Furthermore, fine-tuning of immune responses via mechanical properties of the cells could provide a precise regulation of immune activity based on the specific characteristics of pathological processes.

1. Acuto O. T-cell virtuosity in ‘‘knowing thyself ”. Front. Immunol., 2024, Vol. 15, 1343575. doi: 10.3389/fimmu.2024.1343575.

2. Alatoom A., ElGindi M., Sapudom J., Teo J.C.M. The T Cell Journey: A Tour de Force. Adv. Biol., 2023, Vol. 7, no. 1, 2200173. doi: 10.1002/adbi.202200173.

3. Angeli V., Lim H.Y. Biomechanical control of lymphatic vessel physiology and functions. Cell. Mol. Immunol., 2023, Vol. 20, no. 9, pp. 1051-1062.

4. Bai J., Yan M., Xu Y., Wang Y., Yao Y., Jin P., Zhang Y., Qu Y., Niu L., Li H. YAP enhances mitochondrial OXPHOS in tumor-infiltrating Treg through upregulating Lars2 on stiff matrix. J. Immunother. Cancer, 2024, Vol. 12, no. 11, e010463. doi: 10.1136/jitc-2024-010463.

5. Bergert M., Erzberger A., Desai R.A., Aspalter I.M., Oates A.C., Charras G., Salbreux G., Paluch E.K. Force transmission during adhesion-independent migration. Nat. Cell. Biol., 2015, Vol. 17, no. 4, pp. 524-529.

6. Bertoni A., Alabiso O., Galetto A., Baldanzi G. Integrins in T cell physiology. Int. J. Mol. Sci., 2018, Vol. 19, no. 2, 485. doi: 0.3390/ijms19020485.

7. Boesen E.I., Kakalij R.M. Autoimmune-mediated renal disease and hypertension. Clin. Sci., 2021, Vol. 135, no. 17, pp. 2165-2196.

8. Brosinsky P., Leister H., Cheng N., Varelas X., Visekruna A., Luu M. Verteporfin protects against Th17 cell‐ mediated EAE independently of YAP inhibition. Eur. J. Immunol., 2022, Vol. 52, no. 9, pp. 1523-1526.

9. Cai X., Wang K.C., Meng Z. Mechanoregulation of YAP and TAZ in cellular homeostasis and disease progression. Front. Cell Dev. Biol., 2021, Vol. 9, 673599. doi: 0.3389/fcell.2021.673599.

10. Calvo V., Izquierdo M. Role of actin cytoskeleton reorganization in polarized secretory traffic at the immunological synapse. Front. Cell Dev. Biol., 2021, Vol. 9, 629097. doi: 10.3389/fcell.2021.629097.

11. Cheever A., Townsend M., O’Neill K. Tumor microenvironment immunosuppression: a roadblock to CAR T-cell advancement in solid tumors. Cells, 2022, Vol. 11, no, 22, 3626. doi: 10.3390/cells11223626.

12. Chen D.S. Immunity as biophysics at the surface of a T cell. Immunity, 2024, Vol. 57, no. 2, pp.193-195.

13. Coste B., Mathur J., Schmidt M., Earley T.J., Ranade S., Petrus M.J., Dubin A.E., Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science, 2010, Vol. 330, no. 6000, pp. 55-60.

14. de Jesus M., Settle A.H., Vorselen D., Gaetjens T.K., Galiano M., Wong Y.Y., Fu T.M., Santosa E., Winer B.Y., Tamzalit F., Wang M.S., Bao Z., Sun J.C., Shah P., Theriot J.A., Abel S.M., Huse M. Topographical analysis of immune cell interactions reveals a biomechanical signature for immune cytolysis. Biorxiv, 2023, 2023.04.16.537078. doi: 10.1101/2023.04.16.537078.

15. De Marco R.C., Monzo H.J., Ojala P.M. CAR T cell therapy: a versatile living drug. Int. J Mol. Sci., 2023, Vol. 24, no. 7, 6300. doi: 10.3390/ijms24076300.

16. Douanne T., Griffiths G.M. Cytoskeletal control of the secretory immune synapse. Curr. Opin. Cell Biol., 2021, Vol. 71, pp. 87-94.

17. Du H., Bartleson J.M., Butenko S., Alonso V., Liu W.F., Winer D.A., Butte M.J. Tuning immunity through tissue mechanotransduction. Nat. Rev. Immunol., 2023, Vol. 23, no. 3, pp. 174-188.

18. Fang X.Z., Zhou T., Xu J.Q., Wang Y.X., Sun M.M., He Y.J., Pan S.W., Xiong W., Peng Z.K., Gao X.H., Shang Y. Structure, kinetic properties and biological function of mechanosensitive Piezo channels. Cell Biosci., 2021, Vol. 11, no. 1, 13. doi: 10.1186/s13578-020-00522-z.

19. Fu D., Xie D., Wang F., Chen B., Wang Z., Peng F. Mechanically optimize T cells activation by spiky nanomotors. Front. Bioeng. Biotechnol., 2022, Vol. 10, 844091. doi: 10.3389/fbioe.2022.844091.

20. Ge H., Tian M., Pei Q., Tan F., Pei H. Extracellular matrix stiffness: new areas affecting Cell metabolism. Front. Oncol., 2021, Vol. 11, 631991. doi: 10.3389/fonc.2021.631991.

21. Geng L., Zhang C., He C., Zhang K., Kan H., Mao A., Ma X. Physiological levels of fluid shear stress modulate vascular function through TRPV4 sparklets. Acta Biochim. Biophys. Sin., 2022, Vol. 54, no. 9, pp. 1268-1277.

22. Geng X., Ho Y. C., Srinivasan R.S. Biochemical and mechanical signals in the lymphatic vasculature. Cell. Mol. Life Sci., 2021, Vol. 78, no. 16, pp. 5903-5923.

23. Govendir M.A., Kempe D., Sianati S., Cremasco J., Mazalo J.K., Colakoglu F., Golo M., Poole K., Biro M. T cell cytoskeletal forces shape synapse topography for targeted lysis via membrane curvature bias of perforin. Developmental. Cell., 2022, Vol. 57, no. 18, pp. 2237-2247.

24. Graham K., Lienau P., Bader B., Prechtl S., Naujoks J., Lesche R., Weiske J., Kuehnlenz J., Brzezinka K., Potze L., Zanconato F., Nicke B., Montebaur A., Bone W., Golfier S., Kaulfuss S., Kopitz C., Pilari S., Steuber H., Hayat S., Kamburov A., Steffen A., Schlicker A., Buchgraber P., Braeuer N., Font N.A., Heinrich T., Kuhnke L., Nowak-Reppel K., Stresemann C., Steigemann P., Walter A.O., Blotta S., Ocker M., Lakner A., von Nussbaum F., Mumberg D., Eis K., Piccolo S., Lange M.Discovery of YAP1/TAZ pathway inhibitors through phenotypic screening with potent anti-tumor activity via blockade of Rho-GTPase signaling. Cell Chem. Biol. 2024, Vol. 31, no. 7, pp. 1247-1263.

25. Gunzer M., Schäfer A., Borgmann S., Grabbe S., Zänker K.S., Bröcker E.B., Kämpgen E., Friedl P. Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity, 2000, Vol. 13, no. 3, pp. 323-332.

26. Guo T., He C., Venado A., Zhou Y. Extracellular matrix stiffness in lung health and disease. Compr. Physiol., 2022, Vol. 12, no. 3, pp. 3523-3558.

27. Guo T., Wantono C., Tan Y., Deng F., Duan T., Liu D. Regulators, functions, and mechanotransduction pathways of matrix stiffness in hepatic disease. Front. Physiol., 2023, Vol. 14, 1098129. doi: 10.3389/fphys.2023.1098129.

28. Eiring P., Vashist N., Wedekink F., Genssler S., Fischer B., Dahlhoff J., Mokhtari F., Kuzkina A., Welters M.J.P., Benz T.M., Sorger L., Thiemann V., Almanzar G., Selle M., Thein K., Späth J., Gonzalez M.C., Reitinger C., IpsenEscobedo A., Wistuba-Hamprecht K., Eichler K., Filipski K., Zeiner P.S., Beschorner R., Goedemans R., Gogolla F.H., Hackl H., Rooswinkel R.W., Thiem A., Roche P.R., Joshi H., Pühringer D., Wöckel A., Diessner J.E., Rüdiger M., Leo E., Cheng P.F., Levesque M.P., Goebeler M., Sauer M., Nimmerjahn F., Schuberth-Wagner C., von Felten S., Mittelbronn M., Mehling M., Beilhack A., van der Burg S.H., Riedel A., Weide B., Dummer R., Wischhusen J. Tumorderived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment. Nat. Commun., 2023, Vol. 14, no. 1, 4253. doi: 10.1038/s41467-023-39817-3.

29. Hagenbeek T.J., Zbieg J.R., Hafner M., Mroue R., Lacap J.A., Sodir N.M., Noland C.L., Afghani S., Kishore A., Bhat K.P., Yao X., Schmidt S., Clausen S., Steffek M., Lee W., Beroza P., Martin S., Lin E., Fong R., Di Lello P., Kubala M.H., Yang M.N., Lau J.T., Chan E., Arrazate A., An L., Levy E., Lorenzo M.N., Lee H.J., Pham T.H., Modrusan Z., Zang R., Chen Y.C., Kabza M., Ahmed M., Li J., Chang M.T., Maddalo D., Evangelista M., Ye X., Crawford J.J., Dey A. An allosteric pan-TEAD inhibitor blocks oncogenic YAP/TAZ signaling and overcomes KRAS G12C inhibitor resistance. Nat. Cancer, 2023, Vol. 4, no. 6, pp. 812-828.

30. Hasegawa K., Fujii S., Matsumoto S., Tajiri Y., Kikuchi A., Kiyoshima T. YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation. J. Pathol., 2021, Vol. 253, no. 1, pp. 80-93.

31. Hope J.M., Dombroski J.A., Pereles R.S., Lopez-Cavestany M., Greenlee J.D., Schwager S.C., ReinhartKing C.A., King M.R. Fluid shear stress enhances T cell activation through Piezo1. BMC Biol., 2022, Vol. 20, no. 1, 61. doi: 10.1186/s12915-022-01266-7.

32. Humphries J.D., Chastney M.R., Askari J.A., Humphries M.J. Signal transduction via integrin adhesion complexes. Curr. Opin. Cell Biol., 2019, Vol. 56, pp. 14-21.

33. Huttenlocher A., Horwitz A.R. Integrins in cell migration. Cold Spring Harb. Perspect. Biol., 2011, Vol. 3, no. 9, a005074. doi: 10.1101/cshperspect.a005074

34. Hyun J., Kim S.J., Cho S.D., Kim H.W.Mechano-modulation of T cells for cancer immunotherapy. Biomaterials, 2023, Vol. 297, 122101. doi: 10.1016/j.biomaterials.2023.122101.

35. Jiang W., Wijerathne T.D., Zhang H., Lin Y.C., Jo S., Im W., Lacroix J.J., Luo Y.L. Structural and thermodynamic framework for PIEZO1 modulation by small molecules. Proc. Natl. Acad. Sci. USA, 2023, Vol. 120, no. 50, e2310933120. doi: 0.1073/pnas.2310933120.

36. Jiang Y., Yang X., Jiang J., Xiao B. Structural designs and mechanogating mechanisms of the mechanosensitive piezo channels. Trends Biochem. Sci., 2021, Vol. 46, no. 6, pp. 472-488.

37. Jin W., Tamzalit F., Chaudhuri P.K., Black C.T., Huse M., Kam L.C. T cell activation and immune synapse organization respond to the microscale mechanics of structured surfaces. Proc. Natl. Acad. Sci. USA, 2019, Vol. 116, no. 40, pp. 19835-19840.

38. Jung P., Zhou X., Iden S., Bischoff M., Qu B. T cell stiffness is enhanced upon formation of immunological synapse. Elife, 2021, Vol. 10, e66643. doi: 0.7554/eLife.66643.

39. Kastan N., Gnedeva K., Alisch T., Petelski A.A., Huggins D.J., Chiaravalli J., Aharanov A., Shakked A., Tzahor E., Nagiel A., Segil N., Hudspeth A.J. Small-molecule inhibition of Lats kinases may promote Yap-dependent proliferation in postmitotic mammalian tissues. Nat. Commun., 2021, Vol. 12, no. 1, 3100. doi: 10.1038/s41467-021-23395-3.

40. Kastan N.R., Oak S., Liang R., Baxt L., Myers R.W., Ginn J., Liverton N., Huggins D.J., Pichardo J., Paul M., Carroll T.S., Nagiel A., Gnedeva K., Hudspeth A.J. Development of an improved inhibitor of Lats kinases to promote regeneration of mammalian organs. Proc. Natl. Acad. Sci. USA, 2022, Vol. 119, no. 28, e2206113119. doi: 0.1073/pnas.2206113119.

41. Kim T.J. Mechanobiology: A new frontier in biology. Biology, 2021, Vol. 10, no. 7, 570. doi: 10.3390/biology10070570.

42. Kinsella J.A., Debant M., Parsonage G., Morley L.C., Bajarwan M., Revill C., Foster R., Beech D.J. Pharmacology of PIEZO1 channels. Br. J. Pharmacol., 2024, Vol. 181, no. 23, pp. 4714-4732.

43. Kolasangiani R., Bidone T.C., Schwartz M.A. Integrin conformational dynamics and mechanotransduction. Cells, 2022, Vol. 11, no. 22, 3584. doi: 10.3390/cells11223584.

44. Koo J.H., Guan K.L. Interplay between YAP/TAZ and metabolism. Cell Metab., 2018, Vol. 28, no. 2, pp. 196-206.

45. Lämmermann T., Bader B.L., Monkley S.J., Worbs T., Wedlich-Söldner R., Hirsch K., Keller M., Förster R., Critchley D.R., Fässler R., Sixt M. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature, 2008, Vol. 453, no. 7191, pp. 51-55.

46. Lebid A., Chung L., Pardoll D.M., Pan F. YAP attenuates CD8 T cell-mediated anti-tumor response. Front. Immunol., 2020, Vol. 11, 580. doi: 10.3389/fimmu.2020.00580.

47. Lei K., Kurum A., Kaynak M., Bonati L., Han Y., Cencen V., Gao M., Xie Y.Q., Guo Y., Hannebelle M.T.M., Wu Y., Zhou G., Guo M., Fantner G.E., Sakar M.S., Tang L. Cancer-cell stiffening via cholesterol depletion enhances adoptive T-cell immunotherapy. Nat. Biomed. Eng., 2021. Vol. 5, no. 12, pp. 1411-1425.

48. Liu B., Kolawole E.M., Evavold B.D. Mechanobiology of T cell activation: to catch a bond. Annu Rev. Cell Dev. Biol., 2021, Vol. 37, no. 1, pp. 65-87.

49. Liu C.S.C., Mandal T., Biswas P., Hoque M.A., Bandopadhyay P., Sinha B.P., Sarif J., D’Rozario R., Sinha D.K., Sinha B., Ganguly D. Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells. eLife, 2024, Vol. 12, RP91903. doi: 10.7554/eLife.91903.

50. Liu S., Pan X., Cheng W., Deng B., He Y., Zhang L., Ning Y., Li J. Tubeimoside I antagonizes Yoda1-Evoked Piezo1 channel activation. Front. Pharmacol., 2020, Vol. 11, 768. doi: 10.3389/fphar.2020.00768.

51. Luthold C., Hallal T., Labbé D.P., Bordeleau F. The Extracellular matrix stiffening: a trigger of prostate cancer progression and castration resistance? Cancers, 2022, Vol. 14, no, 12, 2887. doi: 10.3390/cancers14122887.

52. Lv D., Fei Y., Chen H., Wang J., Han W., Cui B., Feng Y., Zhang P., Chen J. Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment. Front. Immunol., 2024, Vol. 15, 1340702. doi: 10.3389/fimmu.2024.1340702.

53. Mancuso R.V., Schneider G., Hürzeler M., Gut M., Zurflüh J., Breitenstein W., Bouitbir J., Reisen F., Atz K., Ehrhardt C., Duthaler U., Gygax D., Schmidt A.G., Krähenbühl S., Weitz-Schmidt G. Allosteric targeting resolves limitations of earlier LFA-1 directed modalities. Biochem. Pharmacol., 2023, Vol. 211, 115504. doi: 10.1016/j.bcp.2023.115504.

54. Martino F., Perestrelo A.R., Vinarský V., Pagliari S., Forte G. Cellular mechanotransduction: from tension to function. Front. Physiol, 2018, Vol. 9, 824. doi: 10.3389/fphys.2018.00824.

55. Meng K.P., Majedi F.S., Thauland T.J., Butte M.J. Mechanosensing through YAP controls T cell activation and metabolism. J. Exp. Med., 2020, Vol. 217, no. 8, e20200053. doi: 10.1084/jem.20200053.

56. Mierke C.T. Extracellular matrix cues regulate mechanosensing and mechanotransduction of cancer cells. Cells, 2024, Vol. 13, no. 1, 96. doi: 10.3390/cells13010096.

57. Montironi C., Muñoz-Pinedo C., Eldering E. Hematopoietic versus solid cancers and T cell dysfunction: looking for similarities and distinctions. Cancers, 2021, Vol. 13, no. 2, 284. doi: 10.3390/cancers13020284

58. Murugesan S., Hong J., Yi J., Li D., Beach J.R., Shao L., Meinhardt J., Madison G., Wu X., Betzig E., Hammer J.A. Formin-generated actomyosin arcs propel T cell receptor microcluster movement at the immune synapse. J. Cell Biol., 2016, Vol. 215, no. 3, pp. 383-399.

59. Narciso M., Martínez Á., Júnior C., Díaz-Valdivia N., Ulldemolins A., Berardi M., Neal K., Navajas D., Farré R., Alcaraz J., Almendros I., Gavara N. Lung Micrometastases Display ECM Depletion and Softening While Macrometastases Are 30-Fold Stiffer and Enriched in Fibronectin. Cancers, 2023, Vol. 15, no. 8, 2404. doi: 10.3390/cancers15082404.

60. Nelson C.M., Xiao B., Wickström S.A., Dufrêne Y.F., Cosgrove D.J., Heisenberg C.P., Dupont S., Shyer A.E., Rodrigues A.R., Trepat X., Diz-Muñoz A. Mechanobiology: Shaping the future of cellular form and function. Cell, 2024, Vol. 187, no. 11, pp. 2652-2656.

61. Ni X., Tao J., Barbi J., Chen Q., Park B.V., Li Z., Zhang N., Lebid A., Ramaswamy A., Wei P., Zheng Y., Zhang X., Wu X., Vignali P., Yang C.P., Li H., Pardoll D., Lu L., Pan D., Pan F. YAP Is Essential for Treg-Mediated Suppression of Antitumor Immunity. Cancer Discov., 2018, Vol. 8, no. 8, pp. 1026-1043.

62. Nicolas N., De Tilly A., Roux E. Blood shear stress during the cardiac cycle and endothelial cell orientation and polarity in the carotid artery of male and female mice. Front. Physiol., 2024, Vol. 15, 1386151. doi: 10.3389/fphys.2024.1386151.

63. Pang R., Sun W., Yang Y., Wen D., Lin F., Wang D., Li K., Zhang N., Liang J., Xiong C., Liu Y. PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes. Nat. Biomed. Eng., 2024, Vol. 8, no. 9, pp. 1162-1176.

64. Pang X., He X., Qiu Z., Zhang H., Xie R., Liu Z., Gu Y., Zhao N., Xiang Q., Cui Y. Targeting integrin pathways: mechanisms and advances in therapy. Sig. Transduct. Target Ther., 2023, Vol. 8, no. 1, 1. doi: 10.1038/s41392-022-01259-6.

65. Pathni A., Özçelikkale A., Rey-Suarez I., Li L., Davis S., Rogers N., Xiao Z., Upadhyaya A. Cytotoxic T lymphocyte activation signals modulate cytoskeletal dynamics and mechanical force generation. Front. Immunol., 2022, Vol. 13, 779888. doi: 10.3389/fimmu.2022.779888.

66. Pathni A., Wagh K., Rey-Suarez I., Upadhyaya A. Mechanical regulation of lymphocyte activation and function. J. Cell Sci., 2024, Vol. 137, no. 13, jcs219030. doi: 10.1242/jcs.219030.

67. Pocaterra A., Romani P., Dupont S. YAP/TAZ functions and their regulation at a glance. J. Cell Sci., 2020, Vol. 133, no. 2, jcs230425. doi: 10.1242/jcs.230425/

68. Pribila J.T., Quale A.C., Mueller K.L., Shimizu Y. Integrins and T cell–mediated immunity. Annu Rev. Immunol., 2004, Vol. 22, no. 1, pp. 157-180.

69. Reversat A., Gaertner F., Merrin J., Stopp J., Tasciyan S., Aguilera J., de Vries I., Hauschild R., Hons M., Piel M., Callan-Jones A., Voituriez R., Sixt M. Cellular locomotion using environmental topography. Nature, 2020, Vol. 582, no. 7813, pp. 582-585.

70. Rogers J., Bajur A.T., Salaita K., Spillane K.M. Mechanical control of antigen detection and discrimination by T and B cell receptors. Biophys. J., 2024, Vol. 123, no. 15, pp. 2234-2255.

71. Rømer A.M.A., Thorseth M.L., Madsen D.H. Immune modulatory properties of collagen in cancer. Front. Immunol., 2021, Vol. 12, 791453. doi: 10.3389/fimmu.2021.791453.

72. Roy N.H., Kim S.H.J., Buffone A.Jr., Blumenthal D., Huang B., Agarwal S., Schwartzberg P.L., Hammer D.A., Burkhardt J.K. LFA-1 signals to promote actin polymerization and upstream migration in T cells J. Cell Sci., 2020, Vol. 133, no. 17, jcs248328. doi: 0.1242/jcs.248328.

73. Sapudom J., Alatoom A., Tipay P.S., Teo J. Cm. Matrix stiffening from collagen fibril density and alignment modulates YAP-mediated T-cell immune suppression. Biomaterials, 2025, Vol. 315, 122900. doi: 10.1016/j.biomaterials.2024.122900.

74. Sarna N.S., Desai S.H., Kaufman B.G., Curry N.M., Hanna A.M., King M.R. Enhanced and sustained T cell activation in response to fluid shear stress. iScience, 2024, Vol. 27, no. 6, 109999. doi: 10.1016/j.isci.2024.109999.

75. Schoppmeyer R., van Steen A.C.I., Kempers L., Timmerman A.L., Nolte M.A., Hombrink P., van Buul J.D. The endothelial diapedesis synapse regulates transcellular migration of human T lymphocytes in a CX3CL1- and SNAP23-dependent manner. Cell Rep., 2022, Vol. 38, no. 3, 110243. doi: 10.1016/j.celrep.2021.110243

76. Secondino S., Canino C., Alaimo D., Muzzana M., Galli G., Borgetto S., Basso S., Bagnarino J., Pulvirenti C., Comoli P., Pedrazzoli P. Clinical trials of cellular therapies in solid tumors. Cancers, 2023, Vol. 15, no. 14, 3667. doi: 10.3390/cancers15143667.

77. Seo J., Kim J. Regulation of Hippo signaling by actin remodeling. BMB Rep., 2018, Vol. 51, no. 3, pp. 151-156.

78. Shalhout S.Z., Yang P.Y., Grzelak E.M., Nutsch K., Shao S., Zambaldo C., Iaconelli J., Ibrahim L., Stanton C., Chadwick S.R., Chen E., DeRan M., Li S., Hull M., Wu X., Chatterjee A.K., Shen W., Camargo F.D., Schultz P.G., Bollong M.J. YAP-dependent proliferation by a small molecule targeting annexin A2. Nat. Chem. Biol., 2021, Vol. 17, no. 7, pp. 767-775.

79. Smith A., Stanley P., Jones K., Svensson L., McDowall A., Hogg N. The role of the integrin LFA‐1 in T‐lymphocyte migration. Immunol. Rev., 2007, Vol. 218, no. 1, pp. 135-146.

80. Sturbaut M., Bailly F., Coevoet M., Sileo P., Pugniere M., Liberelle M., Magnez R., Thuru X., ChartierHarlin M.C., Melnyk P., Gelin M., Allemand F., Guichou J.F., Cotelle P. Discovery of a cryptic site at the interface 2 of TEAD – Towards a new family of YAP/TAZ-TEAD inhibitors. Eur. J. Med. Chem., 2021, Vol. 226, 113835. doi: 10.1016/j.ejmech.2021.113835.

81. Sun D., Shi X., Li S., Wang X., Yang X., Wan M. CAR-T cell therapy: A breakthrough in traditional cancer treatment strategies (Review). Mol. Med. Rep., 2024, Vol. 29, no. 3, 47. doi: 10.3892/mmr.2024.13171.

82. Sundqvist K.G. T cell motility: how is it regulated? Front. Immunol., 2020, Vol. 11, 588642. doi: 10.3389/fimmu.2020.588642.

83. Tamzalit F., Wang M.S., Jin W., Tello-Lafoz M., Boyko V., Heddleston J.M., Black C.T., Kam L.C., Huse M. Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells. Sci. Immunol., 2019, Vol. 4, no. 33, eaav5445. doi: 10.1126/sciimmunol.aav5445.

84. Tang H., Zeng R., He E., Zhang I., Ding C., Zhang A. Piezo-Type mechanosensitive ion Channel Component 1 (Piezo 1): A promising therapeutic target and its modulators: Miniperspective. J. Med. Chem., 2022, Vol. 65, no. 9, pp. 6441-6453.

85. Taylor E.B., Wolf V.L., Dent E., Ryan M.J. Mechanisms of hypertension in autoimmune rheumatic diseases. Br. J. Pharmacol., 2019, Vol. 176, no. 12, pp. 1897-1913.

86. Thien N.D., Hai-Nam N., Anh D.T., Baecker D. Piezo1 and its inhibitors: Overview and perspectives. European J. Med. Chem., 2024, Vol. 273, 116502. doi: 10.1016/j.ejmech.2024.116502.

87. Walling B.L., Kim M. LFA-1 in T Cell Migration and Differentiation. Front. Immunol., 2018, Vol. 9, 952. doi: 10.3389/fimmu.2018.00952.

88. Wang H.J., Wang Y., Mirjavadi S.S., Andersen T., Moldovan L., Vatankhah P., Russell B., Jin J., Zhou Z., Li Q., Cox C.D., Su Q.P., Ju L.A. Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution. Nat. Commun., 2024, Vol. 15, no. 1, 5521. doi: 10.1038/s41467-024-49833-6.

89. Wang M.S., Hu Y., Sanchez E.E., Xie X., Roy N.H., de Jesus M., Winer B.Y., Zale E.A., Jin W., Sachar C., Lee J.H., Hong Y., Kim M., Kam L.C., Salaita K., Huse M. Mechanically active integrins target lytic secretion at the immune synapse to facilitate cellular cytotoxicity. Nat. Commun., 2022, Vol. 13, no. 1, 3222. doi: 10.1038/s41467-022-30809-3.

90. Wijerathne T.D., Ozkan A.D., Lacroix J.J. Yoda1’s energetic footprint on Piezo1 channels and its modulation by voltage and temperature. Proc. Natl. Acad. Sci. USA, 2022, Vol. 119, no. 29, e2202269119. doi: 10.1073/pnas.2202269119.

91. Winkler J., Abisoye-Ogunniyan A., Metcalf K.J., Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat. Commun., 2020, Vol. 11, no. 1, 5120. doi: 10.1038/s41467-020-18794-x.

92. Wong D.C.P., Ding J.L. The mechanobiology of NK cells – ‘Forcing NK to Sense’ target cells. Biochim. Biophys. Acta Rev. Cancer, 2023, Vol. 1878, no. 2, 188860. doi: 10.1016/j.bbcan.2023.188860

93. Woolf E., Grigorova I., Sagiv A., Grabovsky V., Feigelson S. W., Shulman Z., Hartmann T., Sixt M., Cyster J.G., Alon R. Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces. Nat. Immunol., 2007, Vol. 8, no. 10, pp. 1076-1085.

94. Wu J., Lewis A. H., Grandl J. Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels. Trends Biochem. Sci., 2017, Vol. 42, no. 1, pp. 57-71.

95. Xie D., Fu D., Fu S., Chen B., He W., Wilson D.A., Peng F. Mechanical activation of immune T cells via a water driven nanomotor. Adv. Healthc.Mater., 2022, Vol. 11, no. 12, 2200042. doi: 10.1002/adhm.202200042.

96. Yang C., Xie R., Cao T., Zhang Y., Xe Y., Fan Q., Wang X., Ye F. Mechanical communication and function regulation of immune cells. Fundam. Res., 2024, S2667325824001523. doi: 10.1016/j.fmre.2024.04.008.

97. Yang X., Lin C., Chen X., Li S., Li X., Xiao B. Structure deformation and curvature sensing of PIEZO1 in lipid membranes. Nature, 2022, Vol. 604, no. 7905, pp. 377-383.

98. Yong J., Li Y., Lin S., Wang Z., Xu Y. Inhibitors targeting YAP in gastric cancer: current status and future perspectives. Drug Des. Devel. Ther., 2021, Vol. 15, pp. 2445-2456.

99. Yuan D. J., Shi L., Kam L.C. Biphasic response of T cell activation to substrate stiffness. Biomaterials, 2021, Vol. 273, 120797. doi: 0.1016/j.biomaterials.2021.120797.

100. Zagiel B., Melnyk P., Cotelle P. Progress with YAP/TAZ-TEAD inhibitors: a patent review (2018-present). Expert Opin. Ther. Pat., 2022, Vol. 32, no. 8, pp. 899-912. doi: 10.1080/13543776.2022.2096436.

101. Zhao B., Pobbati A.V., Rubin B.P., Stauffer S. Leveraging Hot Spots of TEAD–coregulator interactions in the design of direct small molecule protein-protein interaction disruptors targeting hippo pathway signaling. Pharmaceuticals, 2023, Vol. 16, no. 4, p. 583. doi: 10.3390/ph16040583.

102. Zhou Z., Martinac B. Mechanisms of PIEZO Channel Inactivation. Int. J Mol. Sci., 2023, Vol. 24, no. 18, 14113. doi: 10.3390/ijms241814113.

103. Zhu B., Qian W., Han C., Bai T., Hou X. Piezo 1 activation facilitates cholangiocarcinoma metastasis via Hippo/YAP signaling axis. Mol.Ther. Nucleic Acids, 2021, Vol. 24, pp. 241-252.

104. Zhuang C., Gould J.E., Enninful A., Shao S., Mak M. Biophysical and mechanobiological considerations for T-cell-based immunotherapy. Trends Pharmacol. Sci., 2023, Vol. 44, no. 6, pp. 366-378.

105. Zimmerman T., Blanco F. Inhibitors Targeting the LFA-1/ICAM-1 Cell-Adhesion Interaction: Design and Mechanism of Action. Curr. Pharm. Des., 2008, Vol. 14, no. 22, pp. 2128-2139.

106. Zuidema A., Wang W., Sonnenberg A. Crosstalk between Cell Adhesion Complexes in Regulation of Mechanotransduction. BioEssays, 2020, Vol. 42, no. 11, 2000119. doi: 10.1002/bies.202000119.