Biophysical Reviews

, Volume 11, Issue 3, pp 311–318 | Cite as

Tensile and compressive force regulation on cell mechanosensing

  • Yunfeng Chen
  • Zhiyong Li
  • Lining Arnold JuEmail author


Receptor-mediated cell mechanosensing plays critical roles in cell spreading, migration, growth, and survival. Dynamic force spectroscopy (DFS) techniques have recently been advanced to visualize such processes, which allow the concurrent examination of molecular binding dynamics and cellular response to mechanical stimuli on single living cells. Notably, the live-cell DFS is able to manipulate the force “waveforms” such as tensile versus compressive, ramped versus clamped, static versus dynamic, and short versus long lasting forces, thereby deriving correlations of cellular responses with ligand binding kinetics and mechanical stimulation profiles. Here, by differentiating extracellular mechanical stimulations into two major categories, tensile force and compressive force, we review the latest findings on receptor-mediated mechanosensing mechanisms that are discovered by the state-of-the-art live-cell DFS technologies.


Mechanosensing Receptor–ligand interactions Dynamic force spectroscopy Force waveform 



Dynamic force spectroscopy


Atomic force microscopy


Biomembrane force probe


Optical tweezers


T cell receptor


Peptide major histocompatibility complex


von Willebrand factor



We thank Prof. Cheng Zhu for helpful discussion. This work was supported by the Cardiac Society of Australia and New Zealand BAYER Young Investigator Research Grant (L.A.J.). L.A.J. is an Australian Research Council DECRA Fellow (DE190100609) and a former National Heart Foundation of Australia postdoctoral fellow (101798). Y.C. is a MERU (Medolago-Ruggeri) Foundation post-doctoral awardee. Z.L. is an Australian Research Council Future Fellow (FT140101152).

Compliance with ethical standards

Conflict of interest

Yunfeng Chen declares that he has no conflict of interest. Zhiyong Li declares that he has no conflict of interest. Lining Arnold Ju declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Akiyoshi B, Sarangapani KK, Powers AF, Nelson CR, Reichow SL, Arellano-Santoyo H, Gonen T, Ranish JA, Asbury CL, Biggins S (2010) Tension directly stabilizes reconstituted kinetochore-microtubule attachments. Nature 468:576–579CrossRefGoogle Scholar
  2. Bacabac RG, Smit TH, Mullender MG, Dijcks SJ, Van Loon JJ, Klein-Nulend J (2004) Nitric oxide production by bone cells is fluid shear stress rate dependent. Biochem Biophys Res Commun 315:823–829CrossRefGoogle Scholar
  3. Block H, Herter JM, Rossaint J, Stadtmann A, Kliche S, Lowell CA, Zarbock A (2012) Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med 209:407–421CrossRefGoogle Scholar
  4. Brockman JM, Blanchard AT, Pui-Yan VM, Derricotte WD, Zhang Y, Fay ME, Lam WA, Evangelista FA, Mattheyses AL, Salaita K (2018) Mapping the 3D orientation of piconewton integrin traction forces. Nat Meth 15:115–118CrossRefGoogle Scholar
  5. Charras G, Yap AS (2018) Tensile forces and mechanotransduction at cell-cell junctions. Curr Biol 28:R445–R457CrossRefGoogle Scholar
  6. Chaudhuri O, Parekh SH, Fletcher DA (2007) Reversible stress softening of actin networks. Nature 445:295–298CrossRefGoogle Scholar
  7. Chaudhuri O, Gu L, Klumpers D, Darnell M, Bencherif SA, Weaver JC, Huebsch N, Lee HP, Lippens E, Duda GN et al (2016) Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat Mater 15:326–334CrossRefGoogle Scholar
  8. Chen W, Lou J, Evans EA, Zhu C (2012) Observing force-regulated conformational changes and ligand dissociation from a single integrin on cells. J Cell Biol 199:497–512CrossRefGoogle Scholar
  9. Chen Y, Ju L, Rushdi M, Ge C, Zhu C (2017a) Receptor-mediated cell mechanosensing. Mol Biol Cell 28:3134–3155CrossRefGoogle Scholar
  10. Chen Y, Lee H, Tong H, Schwartz M, Zhu C (2017b) Force regulated conformational change of integrin alphaVbeta3. Matrix Biol 60-61:70–85CrossRefGoogle Scholar
  11. Chen Y, Ju LA, Zhou F, Liao J, Xue L, Su QP, Jin D, Yuan Y, Lu H, Jackson SP et al (2019) An integrin alphaIIbbeta3 intermediate affinity state mediates biomechanical platelet aggregation. Nat Mater In pressGoogle Scholar
  12. Cheng G, Tse J, Jain RK, Munn LL (2009) Micro-environmental mechanical stress controls tumor spheroid size and morphology by suppressing proliferation and inducing apoptosis in cancer cells. PLoS One 4:e4632CrossRefGoogle Scholar
  13. Choi YI, Duke-Cohan JS, Chen W, Liu B, Rossy J, Tabarin T, Ju L, Gui J, Gaus K, Zhu C et al (2014) Dynamic control of β1 integrin adhesion by the plexinD1-sema3E axis. Proc Natl Acad Sci U S A 111:379–384CrossRefGoogle Scholar
  14. Comrie WA, Babich A, Burkhardt JK (2015) F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse. J Cell Biol 208:475–491CrossRefGoogle Scholar
  15. Cox CD, Bavi N, Martinac B (2017) Origin of the force: the force-from-lipids principle applied to piezo channels. Curr Top Membr 79:59–96CrossRefGoogle Scholar
  16. Elosegui-Artola A, Oria R, Chen Y, Kosmalska A, Perez-Gonzalez C, Castro N, Zhu C, Trepat X, Roca-Cusachs P (2016) Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat Cell Biol 18:540–548CrossRefGoogle Scholar
  17. Farge E (2003) Mechanical induction of Twist in the Drosophila foregut/stomodeal primordium. Curr Biol 13:1365–1377CrossRefGoogle Scholar
  18. Feghhi S, Tooley WW, Sniadecki NJ (2016) Nonmuscle myosin IIA regulates platelet contractile forces through rho kinase and myosin light-chain kinase. J Biomech Eng 138Google Scholar
  19. Fiore VF, Ju L, Chen Y, Zhu C, Barker TH (2014) Dynamic catch of a Thy-1-alpha5beta1+syndecan-4 trimolecular complex. Nat Commun 5:4886CrossRefGoogle Scholar
  20. Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature 463:485–492CrossRefGoogle Scholar
  21. Fournier MF, Sauser R, Ambrosi D, Meister JJ, Verkhovsky AB (2010) Force transmission in migrating cells. J Cell Biol 188:287–297CrossRefGoogle Scholar
  22. Guo XE, Hung CT, Sandell LJ, Silva MJ (2018) Musculoskeletal mechanobiology: a new era for mechanomedicine. J Orthop Res 36:531–532Google Scholar
  23. Hattrup CL, Gendler SJ (2008) Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol 70:431–457CrossRefGoogle Scholar
  24. Hoffman BD, Yap AS (2015) Towards a dynamic understanding of cadherin-based Mechanobiology. Trends Cell Biol 25:803–814CrossRefGoogle Scholar
  25. Holle AW, Tang X, Vijayraghavan D, Vincent LG, Fuhrmann A, Choi YS, del Alamo JC, Engler AJ (2013) In situ mechanotransduction via vinculin regulates stem cell differentiation. Stem Cells 31:2467–2477CrossRefGoogle Scholar
  26. Hong J, Ge C, Jothikumar P, Yuan Z, Liu B, Bai K, Li K, Rittase W, Shinzawa M, Zhang Y et al (2018) A TCR mechanotransduction signaling loop induces negative selection in the thymus. Nat Immunol 19:1379–1390CrossRefGoogle Scholar
  27. Huang DL, Bax NA, Buckley CD, Weis WI, Dunn AR (2017) Vinculin forms a directionally asymmetric catch bond with F-actin. Science 357:703–706CrossRefGoogle Scholar
  28. Jackson SP, Nesbitt WS, Westein E (2009) Dynamics of platelet thrombus formation. J Thromb Haemost 7:17–20CrossRefGoogle Scholar
  29. Jacques E, Verbelen JP, Vissenberg K (2013) Mechanical stress in Arabidopsis leaves orients microtubules in a ‘continuous’ supracellular pattern. BMC Plant Biol 13:163CrossRefGoogle Scholar
  30. Ju L, Dong J-F, Cruz MA, Zhu C (2013) The N-terminal flanking region of the A1 domain regulates the force-dependent binding of von Willebrand factor to platelet glycoprotein Ibα. J Biol Chem 288:32289–32301CrossRefGoogle Scholar
  31. Ju L, Chen Y, Xue L, Du X, Zhu C (2016) Cooperative unfolding of distinctive mechanoreceptor domains transduces force into signals. Elife 5:e15447CrossRefGoogle Scholar
  32. Ju L, McFadyen JD, Al-Daher S, Alwis I, Chen Y, Tonnesen LL, Maiocchi S, Coulter B, Calkin AC, Felner EI et al (2018) Compression force sensing regulates integrin alphaIIbbeta3 adhesive function on diabetic platelets. Nat Commun 9:1087CrossRefGoogle Scholar
  33. Kanzaki H, Chiba M, Shimizu Y, Mitani H (2002) Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res 17:210–220CrossRefGoogle Scholar
  34. Kim OV, Litvinov RI, Alber MS, Weisel JW (2017) Quantitative structural mechanobiology of platelet-driven blood clot contraction. Nat Commun 8:1274CrossRefGoogle Scholar
  35. Kong F, Garcia AJ, Mould AP, Humphries MJ, Zhu C (2009) Demonstration of catch bonds between an integrin and its ligand. J Cell Biol 185:1275–1284CrossRefGoogle Scholar
  36. Koyama Y, Mitsui N, Suzuki N, Yanagisawa M, Sanuki R, Isokawa K, Shimizu N, Maeno M (2008) Effect of compressive force on the expression of inflammatory cytokines and their receptors in osteoblastic Saos-2 cells. Arch Oral Biol 53:488–496CrossRefGoogle Scholar
  37. Kuwano Y, Spelten O, Zhang H, Ley K, Zarbock A (2010) Rolling on E- or P-selectin induces the extended but not high-affinity conformation of LFA-1 in neutrophils. Blood 116:617–624CrossRefGoogle Scholar
  38. Lam WA, Chaudhuri O, Crow A, Webster KD, Li T-D, Kita A, Huang J, Fletcher DA (2011) Mechanics and contraction dynamics of single platelets and implications for clot stiffening. Nat Mater 10:61–66CrossRefGoogle Scholar
  39. Lee C-Y, Lou J, Wen K-k, McKane M, Eskin SG, Ono S, Chien S, Rubenstein PA, Zhu C, Mcintire LV (2013) Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds. Proc Natl Acad Sci U S A 110:5022–5027CrossRefGoogle Scholar
  40. Li Y, Bhimalapuram P, Dinner AR (2010) Model for how retrograde actin flow regulates adhesion traction stresses. J Phys Condens Matter 22:194113CrossRefGoogle Scholar
  41. Liu B, Chen W, Evavold BD, Zhu C (2014) Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling. Cell 157:357–368CrossRefGoogle Scholar
  42. Liu B, Chen W, Zhu C (2015) Molecular force spectroscopy on cells. Annu Rev Phys Chem 66:427–451CrossRefGoogle Scholar
  43. Luca VC, Kim BC, Ge C, Kakuda S, Wu D, Roein-Peikar M, Haltiwanger RS, Zhu C, Ha T, Garcia KC (2017) Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity. Science 355:1320–1324CrossRefGoogle Scholar
  44. Maksimovic S, Nakatani M, Baba Y, Nelson AM, Marshall KL, Wellnitz SA, Firozi P, Woo SH, Ranade S, Patapoutian A et al (2014) Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509:617–621CrossRefGoogle Scholar
  45. Manibog K, Li H, Rakshit S, Sivasankar S (2014) Resolving the molecular mechanism of cadherin catch bond formation. Nat Commun 5:3941CrossRefGoogle Scholar
  46. Marshall BT, Long M, Piper JW, Yago T, McEver RP, Zhu C (2003) Direct observation of catch bonds involving cell-adhesion molecules. Nature 423:190–193CrossRefGoogle Scholar
  47. Morikis VA, Chase S, Wun T, Chaikof EL, Magnani JL, Simon SI (2017) Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inflamed endothelium under shear flow. Blood 130:2101–2110CrossRefGoogle Scholar
  48. Nakajima R, Yamaguchi M, Kojima T, Takano M, Kasai K (2008) Effects of compression force on fibroblast growth factor-2 and receptor activator of nuclear factor kappa B ligand production by periodontal ligament cells in vitro. J Periodontal Res 43:168–173CrossRefGoogle Scholar
  49. Naruse K (2018) MECHANOMEDICINE: applications of mechanobiology to medical sciences and next-generation medical technologies. J Smooth Muscle Res 54:83–90CrossRefGoogle Scholar
  50. Neuman KC, Nagy A (2008) Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat Methods 5:491–505CrossRefGoogle Scholar
  51. Nordenfelt P, Elliott HL, Springer TA (2016) Coordinated integrin activation by actin-dependent force during T-cell migration. Nat Commun 7:13119CrossRefGoogle Scholar
  52. Orr AW, Helmke BP, Blackman BR, Schwartz MA (2006) Mechanisms of mechanotransduction. Dev Cell 10:11–20CrossRefGoogle Scholar
  53. Pagliara S, Franze K, McClain CR, Wylde GW, Fisher CL, Franklin RJ, Kabla AJ, Keyser UF, Chalut KJ (2014) Auxetic nuclei in embryonic stem cells exiting pluripotency. Nat Mater 13:638–644CrossRefGoogle Scholar
  54. Pang A, Cui Y, Chen Y, Cheng N, Delaney MK, Gu M, Stojanovic-Terpo A, Zhu C, Du X (2018) Shear-induced integrin signaling in platelet phosphatidylserine exposure, microvesicle release, and coagulation. Blood 132:533–543CrossRefGoogle Scholar
  55. Paszek MJ, Boettiger D, Weaver VM, Hammer DA (2009) Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput Biol 5:e1000604CrossRefGoogle Scholar
  56. Paszek MJ, DuFort CC, Rossier O, Bainer R, Mouw JK, Godula K, Hudak JE, Lakins JN, Wijekoon AC, Cassereau L et al (2014) The cancer glycocalyx mechanically primes integrin-mediated growth and survival. Nature 511:319–325CrossRefGoogle Scholar
  57. Pryshchep S, Zarnitsyna VI, Hong J, Evavold BD, Zhu C (2014) Accumulation of serial forces on TCR and CD8 frequently applied by agonist antigenic peptides embedded in MHC molecules triggers calcium in T cells. J Immunol 193:68–76CrossRefGoogle Scholar
  58. Roca-Cusachs P, Conte V, Trepat X (2017) Quantifying forces in cell biology. Nat Cell Biol 19:742–751CrossRefGoogle Scholar
  59. Roest M, Reininger A, Zwaginga JJ, King MR, Heemskerk JW, Biorheology Subcommittee of the, S.S.C.o.t.I (2011) Flow chamber-based assays to measure thrombus formation in vitro: requirements for standardization. J Thromb Haemost 9:2322–2324CrossRefGoogle Scholar
  60. Rosetti F, Chen Y, Sen M, Thayer E, Azcutia V, Herter JM, Luscinskas FW, Cullere X, Zhu C, Mayadas TN (2015) A lupus-associated Mac-1 variant has defects in integrin allostery and interaction with ligands under force. Cell Rep 10:1655–1664CrossRefGoogle Scholar
  61. Sampathkumar A, Krupinski P, Wightman R, Milani P, Berquand A, Boudaoud A, Hamant O, Jonsson H, Meyerowitz EM (2014) Subcellular and supracellular mechanical stress prescribes cytoskeleton behavior in Arabidopsis cotyledon pavement cells. eLife 3:e01967CrossRefGoogle Scholar
  62. Scrimgeour J, McLane LT, Chang PS, Curtis JE (2017) Single-molecule imaging of proteoglycans in the pericellular matrix. Biophys J 113:2316–2320CrossRefGoogle Scholar
  63. Sibener LV, Fernandes RA, Kolawole EM, Carbone CB, Liu F, McAffee D, Birnbaum ME, Yang X, Su LF, Yu W et al (2018) Isolation of a structural mechanism for uncoupling T cell receptor signaling from peptide-MHC binding. Cell 174:672–687 e627CrossRefGoogle Scholar
  64. Strohmeyer N, Bharadwaj M, Costell M, Fassler R, Muller DJ (2017) Fibronectin-bound alpha5beta1 integrins sense load and signal to reinforce adhesion in less than a second. Nat Mater 16:1262–1270CrossRefGoogle Scholar
  65. Su QP, Ju LA (2018) Biophysical nanotools for single-molecule dynamics. Biophys Rev 10:1349–1357CrossRefGoogle Scholar
  66. Sun Z, Costell M, Fassler R (2019) Integrin activation by Talin, kindlin and mechanical forces. Nat Cell Biol 21:25–31CrossRefGoogle Scholar
  67. Sundd P, Gutierrez E, Koltsova EK, Kuwano Y, Fukuda S, Pospieszalska MK, Groisman A, Ley K (2012) ‘Slings’ enable neutrophil rolling at high shear. Nature 488:399–403CrossRefGoogle Scholar
  68. Swaminathan V, Kalappurakkal JM, Mehta SB, Nordenfelt P, Moore TI, Koga N, Baker DA, Oldenbourg R, Tani T, Mayor S et al (2017) Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions. Proc Natl Acad Sci U S A 114:10648–10653CrossRefGoogle Scholar
  69. Tarbell JM, Simon SI, Curry FR (2014) Mechanosensing at the vascular interface. Annu Rev Biomed Eng 16:505–532CrossRefGoogle Scholar
  70. Tokarev AA, Butylin AA, Ataullakhanov FI (2011) Platelet adhesion from shear blood flow is controlled by near-wall rebounding collisions with erythrocytes. Biophys J 100:799–808CrossRefGoogle Scholar
  71. Tovar-Lopez FJ, Rosengarten G, Nasabi M, Sivan V, Khoshmanesh K, Jackson SP, Mitchell A, Nesbitt WS (2013) An investigation on platelet transport during thrombus formation at micro-scale stenosis. PLoS One 8:e74123CrossRefGoogle Scholar
  72. Valignat MP, Theodoly O, Gucciardi A, Hogg N, Lellouch AC (2013) T lymphocytes orient against the direction of fluid flow during LFA-1-mediated migration. Biophys J 104:322–331CrossRefGoogle Scholar
  73. Weinbaum S, Tarbell JM, Damiano ER (2007) The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng 9:121–167CrossRefGoogle Scholar
  74. Wu P, Zhang T, Liu B, Fei P, Cui L, Qin R, Zhu H, Yao D, Martinez RJ, Hu W et al (2019) Mechano-regulation of peptide-MHC class I conformations determines TCR antigen recognition. Mol Cell 73:1015–1027 e7CrossRefGoogle Scholar
  75. Ye F, Hu G, Taylor D, Ratnikov B, Bobkov AA, McLean MA, Sligar SG, Taylor KA, Ginsberg MH (2010) Recreation of the terminal events in physiological integrin activation. J Cell Biol 188:157–173CrossRefGoogle Scholar
  76. Yeh YT, Serrano R, Francois J, Chiu JJ, Li YJ, Del Alamo JC, Chien S, Lasheras JC (2018) Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis. Proc Natl Acad Sci U S A 115:133–138CrossRefGoogle Scholar

Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Molecular Medicine, MERU-Roon Research Center on Vascular BiologyThe Scripps Research InstituteLa JollaUSA
  2. 2.School of Chemistry, Physics and Mechanical EngineeringQueensland University of TechnologyBrisbaneAustralia
  3. 3.Heart Research InstituteSydneyAustralia
  4. 4.School of Aerospace, Mechanical and Mechatronic EngineeringDarlingtonAustralia
  5. 5.Charles Perkins CentreThe University of SydneyCamperdownAustralia

Personalised recommendations