Iskratsch, T., Wolfenson, H. & Sheetz, M. P. Appreciating force and shape-the rise of mechanotransduction in cell biology. Nat. Rev. Mol. Cell Biol. 15, 825–833 (2014).

CAS  Google Scholar 

Dumortier, J. G. et al. Hydraulic fracturing and active coarsening position the lumen of the mouse blastocyst. Science 365, 465–468 (2019).

CAS  Google Scholar 

Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

CAS  Google Scholar 

Swift, J. & Discher, D. E. The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue. J. Cell Sci. 127, 3005–3015 (2014).

CAS  Google Scholar 

Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behaviour in development and regeneration. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).

CAS  Google Scholar 

Wang, N., Tytell, J. D. & Ingber, D. E. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat. Rev. Mol. Cell Biol. 10, 75–82 (2009).

CAS  Google Scholar 

Tajik, A. et al. Transcription upregulation via force-induced direct stretching of chromatin. Nat. Mater. 15, 1287–1296 (2016).

CAS  Google Scholar 

Kirby, T. J. & Lammerding, J. Emerging views of the nucleus as a cellular mechanosensor. Nat. Cell Biol. 20, 373–381 (2018).

CAS  Google Scholar 

Nava, M. M. et al. Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell 181, 800–817.e22 (2020).

CAS  Google Scholar 

Huse, M. Mechanical forces in the immune system. Nat. Rev. Immunol. 17, 679–690 (2017).

CAS  Google Scholar 

Jaalouk, D. E. & Lammerding, J. Mechanotransduction gone awry. Nat. Rev. Mol. Cell Biol. 10, 63–73 (2009).

CAS  Google Scholar 

Paul, C. D., Mistriotis, P. & Konstantopoulos, K. Cancer cell motility: lessons from migration in confined spaces. Nat. Rev. Cancer 17, 131–140 (2017).

CAS  Google Scholar 

Mohammadi, H. & Sahai, E. Mechanisms and impact of altered tumour mechanics. Nat. Cell Biol. 20, 766–774 (2018).

CAS  Google Scholar 

Dufrene, Y. F. & Persat, A. Mechanomicrobiology: how bacteria sense and respond to forces. Nat. Rev. Microbiol. 18, 227–240 (2020).

CAS  Google Scholar 

Roca-Cusachs, P., Conte, V. & Trepat, X. Quantifying forces in cell biology. Nat. Cell Biol. 19, 742–751 (2017).

CAS  Google Scholar 

Campas, O. et al. Quantifying cell-generated mechanical forces within living embryonic tissues. Nat. Methods 11, 183–189 (2014).

CAS  Google Scholar 

Hu, X., Margadant, F. M., Yao, M. & Sheetz, M. P. Molecular stretching modulates mechanosensing pathways. Protein Sci. 26, 1337–1351 (2017).

CAS  Google Scholar 

Stirnemann, G., Giganti, D., Fernandez, J. M. & Berne, B. J. Elasticity, structure, and relaxation of extended proteins under force. Proc. Natl Acad. Sci. USA 110, 3847–3852 (2013).

CAS  Google Scholar 

Cecconi, C., Shank, E. A., Bustamante, C. & Marqusee, S. Direct observation of the three-state folding of a single protein molecule. Science 309, 2057–2060 (2005).

CAS  Google Scholar 

Shank, E. A., Cecconi, C., Dill, J. W., Marqusee, S. & Bustamante, C. The folding cooperativity of a protein is controlled by its chain topology. Nature 465, 637–640 (2010).

CAS  Google Scholar 

Fernandez, J. M. & Li, H. Force-clamp spectroscopy monitors the folding trajectory of a single protein. Science 303, 1674–1678 (2004).

CAS  Google Scholar 

Neupane, K. et al. Direct observation of transition paths during the folding of proteins and nucleic acids. Science 352, 239–242 (2016).

CAS  Google Scholar 

Yu, H., Siewny, M. G., Edwards, D. T., Sanders, A. W. & Perkins, T. T. Hidden dynamics in the unfolding of individual bacteriorhodopsin proteins. Science 355, 945–950 (2017).

CAS  Google Scholar 

Choi, H. K. et al. Watching helical membrane proteins fold reveals a common N-to-C-terminal folding pathway. Science 366, 1150–1156 (2019).

CAS  Google Scholar 

Petrosyan, R., Narayan, A. & Woodside, M. T. Single-molecule force spectroscopy of protein folding. J. Mol. Biol. 433, 167207 (2021).

CAS  Google Scholar 

Bustamante, C., Alexander, L., Maciuba, K. & Kaiser, C. M. Single-molecule studies of protein folding with optical tweezers. Annu. Rev. Biochem. 89, 443–470 (2020).

CAS  Google Scholar 

Schonfelder, J., Alonso-Caballero, A., De Sancho, D. & Perez-Jimenez, R. The life of proteins under mechanical force. Chem. Soc. Rev. 47, 3558–3573 (2018).

CAS  Google Scholar 

Sharma, S., Subramani, S. & Popa, I. Does protein unfolding play a functional role in vivo? FEBS J. 288, 1742–1758 (2021).

CAS  Google Scholar 

Garcia-Manyes, S. & Beedle, A. E. M. Steering chemical reactions with force. Nat. Rev. Chem. 1, s41570-017-0083 (2017).

Google Scholar 

Veigel, C. & Schmidt, C. F. Moving into the cell: single-molecule studies of molecular motors in complex environments. Nat. Rev. Mol. Cell Biol. 12, 163–176 (2011).

CAS  Google Scholar 

Krieg, M. et al. Atomic force microscopy-based mechanobiology. Nat. Rev. Phys. 1, 41–57 (2018).

Google Scholar 

Neuman, K. C. & Nagy, A. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat. Methods 5, 491–505 (2008).

CAS  Google Scholar 

Moffitt, J. R., Chemla, Y. R., Smith, S. B. & Bustamante, C. Recent advances in optical tweezers. Annu. Rev. Biochem. 77, 205–228 (2008).

CAS  Google Scholar 

Yang, B., Liu, Z., Liu, H. & Nash, M. A. Next generation methods for single-molecule force spectroscopy on polyproteins and receptor–ligand complexes. Front. Mol. Biosci. 7, 85 (2020).

CAS  Google Scholar 

Milles, L. F., Schulten, K., Gaub, H. E. & Bernardi, R. C. Molecular mechanism of extreme mechanostability in a pathogen adhesin. Science 359, 1527–1533 (2018).

CAS  Google Scholar 

Milles, L. F. & Gaub, H. E. Extreme mechanical stability in protein complexes. Curr. Opin. Struct. Biol. 60, 124–130 (2020).

CAS  Google Scholar 

Schoeler, C. et al. Ultrastable cellulosome–adhesion complex tightens under load. Nat. Commun. 5, 5635 (2014).

CAS  Google Scholar 

Liu, Z. et al. High force catch bond mechanism of bacterial adhesion in the human gut. Nat. Commun. 11, 4321 (2020).

CAS  Google Scholar 

Herman-Bausier, P. & Dufrene, Y. F. Force matters in hospital-acquired infections. Science 359, 1464–1465 (2018).

CAS  Google Scholar 

Mathelie-Guinlet, M. et al. Force-clamp spectroscopy identifies a catch bond mechanism in a Gram-positive pathogen. Nat. Commun. 11, 5431 (2020).

Google Scholar 

Viela, F., Speziale, P., Pietrocola, G. & Dufrene, Y. F. Mechanostability of the fibrinogen bridge between staphylococcal surface protein ClfA and endothelial cell integrin αVβ3. Nano Lett. 19, 7400–7410 (2019).

CAS  Google Scholar 

Bustamante, C. J., Chemla, Y. R., Liu, S. & Wang, M. D. Optical tweezers in single-molecule biophysics. Nat. Rev. Methods Primers 1, 25 (2021).

CAS  Google Scholar 

Edwards, D. T. et al. Optimizing 1-μs-resolution single-molecule force spectroscopy on a commercial atomic force microscope. Nano Lett. 15, 7091–7098 (2015).

CAS  Google Scholar 

Cecconi, C., Shank, E. A., Marqusee, S. & Bustamante, C. DNA molecular handles for single-molecule protein-folding studies by optical tweezers. Methods Mol. Biol. 749, 255–271 (2011).

CAS  Google Scholar 

Mora, M., Stannard, A. & Garcia-Manyes, S. The nanomechanics of individual proteins. Chem. Soc. Rev. 49, 6816–6832 (2020).

CAS  Google Scholar 

Lof, A. et al. Multiplexed protein force spectroscopy reveals equilibrium protein folding dynamics and the low-force response of von Willebrand factor. Proc. Natl Acad. Sci. USA 116, 18798–18807 (2019).

Google Scholar 

Lu, H. & Schulten, K. The key event in force-induced unfolding of titin’s immunoglobulin domains. Biophys. J. 79, 51–65 (2000).

CAS  Google Scholar 

Franz, F., Daday, C. & Grater, F. Advances in molecular simulations of protein mechanical properties and function. Curr. Opin. Struct. Biol. 61, 132–138 (2020).

CAS  Google Scholar 

Berkovich, R., Garcia-Manyes, S., Urbakh, M., Klafter, J. & Fernandez, J. M. Collapse dynamics of single proteins extended by force. Biophys. J. 98, 2692–2701 (2010).

CAS  Google Scholar 

Smith, S. B., Cui, Y. & Bustamante, C. Overstretching B-DNA: the elastic response of individual double-stranded and single-stranded DNA molecules. Science 271, 795–799 (1996).

CAS  Google Scholar 

Bosco, A., Camunas-Soler, J. & Ritort, F. Elastic properties and secondary structure formation of single-stranded DNA at monovalent and divalent salt conditions. Nucleic Acids Res. 42, 2064–2074 (2014).

CAS  Google Scholar 

Dudko, O. K., Hummer, G. & Szabo, A. Intrinsic rates and activation free energies from single-molecule pulling experiments. Phys. Rev. Lett. 96, 108101 (2006).

Google Scholar 

Stannard, A. et al. Molecular fluctuations as a ruler of force-induced protein conformations. Nano Lett. 21, 2953–2961 (2021).

CAS  Google Scholar 

Li, H., Carrion-Vazquez, M., Oberhauser, A. F., Marszalek, P. E. & Fernandez, J. M. Point mutations alter the mechanical stability of immunoglobulin modules. Nat. Struct. Biol. 7, 1117–1120 (2000).

CAS  Google Scholar 

Carrion-Vazquez, M. et al. The mechanical stability of ubiquitin is linkage dependent. Nat. Struct. Biol. 10, 738–743 (2003).

CAS  Google Scholar 

Brockwell, D. J. et al. Pulling geometry defines the mechanical resistance of a β-sheet protein. Nat. Struct. Biol. 10, 731–737 (2003).

CAS  Google Scholar 

Carl, P., Kwok, C. H., Manderson, G., Speicher, D. W. & Discher, D. E. Forced unfolding modulated by disulfide bonds in the Ig domains of a cell adhesion molecule. Proc. Natl Acad. Sci. USA 98, 1565–1570 (2001).

CAS  Google Scholar 

Wiita, A. P., Ainavarapu, S. R., Huang, H. H. & Fernandez, J. M. Force-dependent chemical kinetics of disulfide bond reduction observed with single-molecule techniques. Proc. Natl Acad. Sci. USA 103, 7222–7227 (2006).

CAS