Skip to main content
Log in

Double-stranded DNA force sensors to study the molecular level forces required to activate signaling pathways

  • Review
  • Published:
Journal of the Korean Physical Society Aims and scope Submit manuscript

Abstract

Single-molecule force measurement techniques provide unique opportunities to investigate simple molecular interactions and complicated force-induced cell responses. This has revolutionized our understanding of how mechanical cues influence cell behaviors. Recent advances in DNA technologies have led to the development of tension sensors for high-throughput screening of pN scale forces with single-molecule precision. Thus, the emerging DNA-based mechano-sensors are replacing conventional single-molecule force spectroscopes. This review provides an overview of double-stranded DNA-based mechano-sensors, such as the tension gauge tether (TGT) and its derivatives, and their biophysical applications. First, we review the theoretical background of the force-induced rupture of DNA duplexes and force sensing mechanisms using DNA structures. Next, we survey the use of double-stranded DNA-based force sensors to study the role of mechanical forces, mostly receptor tensions, in signaling pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. A. Katsumi, A.W. Orr, E. Tzima, M.A. Schwartz, Integrins in mechanotransduction. J. Biol. Chem. 279(13), 12001–12004 (2004)

    Article  Google Scholar 

  2. A. Rokas, The origins of multicellularity and the early history of the genetic toolkit for animal development. Annu. Rev. Genet. 42, 235–251 (2008)

    Article  Google Scholar 

  3. A.F. Palazzo, C.H. Eng, D.D. Schlaepfer, E.E. Marcantonio, G.G. Gundersen, Localized stabilization of microtubules by integrin-and FAK-facilitated Rho signaling. Science 303(5659), 836–839 (2004)

    Article  ADS  Google Scholar 

  4. A.S. Menko, D. Boettiger, Occupation of the extracellular matrix receptor, integrin, is a control point for myogenic differentiation. Cell 51(1), 51–57 (1987)

    Article  Google Scholar 

  5. M.E. Chicurel, C.S. Chen, D.E. Ingber, Cellular control lies in the balance of forces. Curr. Opin. Cell Biol. 10(2), 232–239 (1998)

    Article  Google Scholar 

  6. Y. Liu, K. Galior, V.P.-Y. Ma, K. Salaita, Molecular tension probes for imaging forces at the cell surface. Acc. Chem. Res. 50(12), 2915–2924 (2017)

    Article  Google Scholar 

  7. K. Galior, V.P.Y. Ma, Y. Liu, H. Su, N. Baker, R.A. Panettieri Jr., C. Wongtrakool, K. Salaita, Molecular tension probes to investigate the mechanopharmacology of single cells: a step toward personalized mechanomedicine. Adv. Healthc. Mater. 7(14), 1800069 (2018)

    Article  Google Scholar 

  8. C. Jurchenko, Y. Chang, Y. Narui, Y. Zhang, K.S. Salaita, Integrin-generated forces lead to streptavidin-biotin unbinding in cellular adhesions. Biophys. J. 106(7), 1436–1446 (2014)

    Article  ADS  Google Scholar 

  9. Y. Liu, K. Yehl, Y. Narui, K. Salaita, Tension sensing nanoparticles for mechano-imaging at the living/nonliving interface. J. Am. Chem. Soc. 135(14), 5320–5323 (2013)

    Article  Google Scholar 

  10. Y. Chang, Z. Liu, Y. Zhang, K. Galior, J. Yang, K. Salaita, A general approach for generating fluorescent probes to visualize piconewton forces at the cell surface. J. Am. Chem. Soc. 138(9), 2901–2904 (2016)

    Article  Google Scholar 

  11. Y. Liu, R. Medda, Z. Liu, K. Galior, K. Yehl, J.P. Spatz, E.A. Cavalcanti-Adam, K. Salaita, Nanoparticle tension probes patterned at the nanoscale: impact of integrin clustering on force transmission. Nano Lett. 14(10), 5539–5546 (2014)

    Article  ADS  Google Scholar 

  12. K. Galior, Y. Liu, K. Yehl, S. Vivek, K. Salaita, Titin-based nanoparticle tension sensors map high-magnitude integrin forces within focal adhesions. Nano Lett. 16(1), 341–348 (2016)

    Article  ADS  Google Scholar 

  13. T. Wiegand, M. Fratini, F. Frey, K. Yserentant, Y. Liu, E. Weber, K. Galior, J. Ohmes, F. Braun, D.-P. Herten, Forces during cellular uptake of viruses and nanoparticles at the ventral side. Nat. Commun. 11(1), 1–13 (2020)

    Article  Google Scholar 

  14. M.D. Brenner, R. Zhou, D.E. Conway, L. Lanzano, E. Gratton, M.A. Schwartz, T. Ha, Spider silk peptide is a compact, linear nanospring ideal for intracellular tension sensing. Nano Lett. 16(3), 2096–2102 (2016)

    Article  ADS  Google Scholar 

  15. J.D. Watson, F.H. Crick, Molecular structure of nucleic acids. Nature 171(4356), 737–738 (1953)

    Article  ADS  Google Scholar 

  16. C. Bustamante, Y.R. Chemla, N.R. Forde, D. Izhaky, Mechanical processes in biochemistry. Annu. Rev. Biochem. 73(1), 705–748 (2004)

    Article  Google Scholar 

  17. I. Tinoco Jr., C. Bustamante, The effect of force on thermodynamics and kinetics of single molecule reactions. Biophys. Chem. 101, 513–533 (2002)

    Article  Google Scholar 

  18. J.M. Brockman, K. Salaita, Mechanical proofreading: a general mechanism to enhance the fidelity of information transfer between cells. Front. Phys. 7, 14 (2019)

    Article  Google Scholar 

  19. Y. Zhang, C. Ge, C. Zhu, K. Salaita, DNA-based digital tension probes reveal integrin forces during early cell adhesion. Nat. Commun. 5(1), 1–10 (2014)

    ADS  Google Scholar 

  20. K. Hatch, C. Danilowicz, V. Coljee, M. Prentiss, Demonstration that the shear force required to separate short double-stranded DNA does not increase significantly with sequence length for sequences longer than 25 base pairs. Phys. Rev. E 78(1), 011920 (2008)

    Article  ADS  Google Scholar 

  21. de Gennes P-G (2001) Maximum pull out force on DNA hybrids. arXiv preprint arXiv:physics/0110011

  22. M. Roein-Peikar, Q. Xu, X. Wang, T. Ha, Ultrasensitivity of cell adhesion to the presence of mechanically strong ligands. Phys. Rev. X 6(1), 011001 (2016)

    Google Scholar 

  23. X. Wang, T. Ha, Defining single molecular forces required to activate integrin and notch signaling. Science 340(6135), 991–994 (2013)

    Article  ADS  Google Scholar 

  24. X. Wang, J. Sun, Q. Xu, F. Chowdhury, M. Roein-Peikar, Y. Wang, T. Ha, Integrin molecular tension within motile focal adhesions. Biophys. J. 109(11), 2259–2267 (2015)

    Article  ADS  Google Scholar 

  25. Y. Wang, D.N. LeVine, M. Gannon, Y. Zhao, A. Sarkar, B. Hoch, X. Wang, Force-activatable biosensor enables single platelet force mapping directly by fluorescence imaging. Biosens. Bioelectron. 100, 192–200 (2018)

    Article  Google Scholar 

  26. M.H. Jo, W.T. Cottle, T. Ha, Real-time measurement of molecular tension during cell adhesion and migration using multiplexed differential analysis of tension gauge tethers. ACS Biomater. Sci. Eng. 5, 3856–3863 (2019)

    Article  Google Scholar 

  27. F.G. Giancotti, E. Ruoslahti, Integrin signaling. Science 285(5430), 1028–1033 (1999)

    Article  Google Scholar 

  28. P.M. de Odrowaz, P. Czuba, M. Targosz, K. Burda, M. Szymoński, Dynamic force measurements of avidin-biotin and streptavdin-biotin interactions using AFM. Acta Biochim. Pol. 53(1), 93–100 (2006)

    Article  Google Scholar 

  29. Y. Wang, X. Wang, Integrins outside focal adhesions transmit tensions during stable cell adhesion. Sci. Rep. 6(1), 1–9 (2016)

    Article  Google Scholar 

  30. Z. Rahil, S. Pedron, X. Wang, T. Ha, B. Harley, D. Leckband, Nanoscale mechanics guides cellular decision making. Integr. Biol. 8(9), 929–935 (2016)

    Article  Google Scholar 

  31. M.K. Lee, J. Park, X. Wang, M. Roein-Peikar, E. Ko, E. Qin, J. Lee, T. Ha, H. Kong, Rupture force of cell adhesion ligand tethers modulates biological activities of a cell-laden hydrogel. Chem. Commun. 52, 4757–4760 (2016)

    Article  Google Scholar 

  32. F. Chowdhury, I.T.S. Li, B.J. Leslie, S. Doğanay, R. Singh, X. Wang, J. Seong, S.-H. Lee, S. Park, N. Wang, T. Ha, Single molecular force across single integrins dictates cell spreading. Integr. Biol. 7(10), 1265–1271 (2015)

    Article  Google Scholar 

  33. Y. Zhao, Y. Wang, A. Sarkar, X. Wang, Keratinocytes generate high integrin tension at the trailing edge to mediate rear de-adhesion during rapid cell migration. iScience 9, 502–512 (2018)

    Article  ADS  Google Scholar 

  34. F. Chowdhury, I.T.S. Li, T.T.M. Ngo, B.J. Leslie, B.C. Kim, J.E. Sokoloski, E. Weiland, X. Wang, Y.R. Chemla, T.M. Lohman, T. Ha, Defining single molecular forces required for notch activation using nano yoyo. Nano Lett. 16(6), 3892–3897 (2016)

    Article  ADS  Google Scholar 

  35. V.C. Luca, B.C. Kim, C. Ge, F. Wu, M. Roein-Peikar, R.S. Haltiwanger, C. Zhu, T. Ha, K.C. Garcia, Notch-jagged complex structure implicates a catch bond in tuning ligand sensitivity. Science 355, 1320–1324 (2017)

    Article  ADS  Google Scholar 

  36. I.T.S. Li, T. Ha, Y.R. Chemla, Mapping cell surface adhesion by rotation tracking and adhesion footprinting. Sci. Rep. 7, 44502 (2017)

    Article  ADS  Google Scholar 

  37. V.P.-Y. Ma, Y. Liu, K. Yehl, K. Gailor, Y. Zhang, K. Salaita, Mechanically induced catalytic amplification reaction for readout of receptor mediated cellular forces. Angew. Chem. 55(18), 5488–5492 (2016)

    Article  Google Scholar 

  38. Y. Wang, Y. Zhao, A. Sarkar, X. Wang, Optical sensor revealed abnormal nuclease spatial activity on cancer cell memrane. J. Biophotonics 12(5), e201800351 (2018)

    Google Scholar 

  39. Y. Zhao, A. Sarkar, X. Wang, Peptide nucleic acid based tension sensor for cellular force imaging with strong DNase resistance. Biosens. Bioelectron. 150, 111959 (2020)

    Article  Google Scholar 

Download references

Acknowledgement

This work was supported by the Incheon National University Research Grant in 2017.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Byoung Choul Kim.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, Y., Kim, K.A. & Kim, B.C. Double-stranded DNA force sensors to study the molecular level forces required to activate signaling pathways. J. Korean Phys. Soc. 78, 386–392 (2021). https://doi.org/10.1007/s40042-020-00046-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40042-020-00046-2

Keywords

Navigation