Ingber, D. E. Mechanobiology and diseases of mechanotransduction. Ann. Med. 35, 564–577 (2003).
Hannezo, E. & Heisenberg, C. P. Mechanochemical feedback loops in development and disease. Cell 178, 12–25 (2019).
van Helvert, S., Storm, C. & Friedl, P. Mechanoreciprocity in cell migration. Nat. Cell Biol. 20, 8–20 (2018).
Roca-Cusachs, P., Conte, V. & Trepat, X. Quantifying forces in cell biology. Nat. Cell Biol. 19, 742–751 (2017).
Stewart, M. P. et al. Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding. Nature 469, 226–230 (2011).
Garcia-Arcos, J. M., Jha, A., Waterman, C. M. & Piel, M. Blebology: principles of bleb-based migration. Trends Cell Biol. 34, 838–853 (2024).
Sanfeliu-Cerdan, N. et al. A MEC-2/stomatin condensate liquid-to-solid phase transition controls neuronal mechanotransduction during touch sensing. Nat. Cell Biol. 25, 1590–1599 (2023).
Koser, D. E. et al. Mechanosensing is critical for axon growth in the developing brain. Nat. Neurosci. 19, 1592–1598 (2016). This seminal paper describes a clear function of mechanosensing in the central nervous system in vivo.
Llinares-Benadero, C. & Borrell, V. Deconstructing cortical folding: genetic, cellular and mechanical determinants. Nat. Rev. Neurosci. 20, 161–176 (2019).
Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J. & Shenoy, V. B. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584, 535–546 (2020).
Lomakin, A. J. et al. The nucleus acts as a ruler tailoring cell responses to spatial constraints. Science 370, eaba2894 (2020). This paper describes a novel mechanosensory role of the nucleus in measuring cellular constraints.
Mao, Y. & Wickstrom, S. A. Mechanical state transitions in the regulation of tissue form and function. Nat. Rev. Mol. Cell Biol. 25, 654–670 (2024).
Tyler, W. J. The mechanobiology of brain function. Nat. Rev. Neurosci. 13, 867–878 (2012).
Ladoux, B. & Mege, R. M. Mechanobiology of collective cell behaviours. Nat. Rev. Mol. Cell Biol. 18, 743–757 (2017).
Hofer, M. & Lutolf, M. P. Engineering organoids. Nat. Rev. Mater. 6, 402–420 (2021).
Karzbrun, E. et al. Human neural tube morphogenesis in vitro by geometric constraints. Nature 599, 268–272 (2021). The authors establish the role of mechanical constraints in the formation of complex neural organoids.
Wu, P. H. et al. A comparison of methods to assess cell mechanical properties. Nat. Methods 15, 491–498 (2018).
Vianello, S. & Lutolf, M. P. Understanding the mechanobiology of early mammalian development through bioengineered models. Dev. Cell 48, 751–763 (2019).
Mittelheisser, V. et al. Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases. Nat. Nanotechnol. 19, 281–297 (2024).
Krieg, M. et al. Atomic force microscopy-based mechanobiology. Nat. Rev. Phys. 1, 41–57 (2019).
Neuman, K. C. & Nagy, A. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat. Methods 5, 491–505 (2008).
Catala-Castro, F., Schaffer, E. & Krieg, M. Exploring cell and tissue mechanics with optical tweezers. J. Cell Sci. 136, jcs261843 (2022).
Fischer-Friedrich, E., Hyman, A. A., Julicher, F., Muller, D. J. & Helenius, J. Quantification of surface tension and internal pressure generated by single mitotic cells. Sci. Rep. 4, 6213 (2014).
Tambe, D. T. et al. Collective cell guidance by cooperative intercellular forces. Nat. Mater. 10, 469–475 (2011).
Gavara, N. & Chadwick, R. S. Determination of the elastic moduli of thin samples and adherent cells using conical atomic force microscope tips. Nat. Nanotechnol. 7, 733–736 (2012).
Roffay, C., Chan, C. J., Guirao, B., Hiiragi, T. & Graner, F. Inferring cell junction tension and pressure from cell geometry. Development 148, dev192773 (2021).
Venkova, L. et al. A mechano-osmotic feedback couples cell volume to the rate of cell deformation. eLife 11, e72381 (2022).
Ichbiah, S., Delbary, F., McDougall, A., Dumollard, R. & Turlier, H. Embryo mechanics cartography: inference of 3D force atlases from fluorescence microscopy. Nat. Methods 20, 1989–1999 (2023).
Runser, S., Vetter, R. & Iber, D. SimuCell3D: three-dimensional simulation of tissue mechanics with cell polarization. Nat. Comput. Sci. 4, 299–309 (2024). This paper introduces an advanced multiparametric computational model that enables large-scale, high-resolution simulations of 3D tissue organization and mechanics.
Schillers, H. et al. Standardized nanomechanical atomic force microscopy procedure (SNAP) for measuring soft and biological samples. Sci. Rep. 7, 5117 (2017).
Kollmannsberger, P. & Fabry, B. Linear and nonlinear rheology of living cells. Ann. Rev. Mater. Res. 41, 75–97 (2011).
Rigato, A., Miyagi, A., Scheuring, S. & Rico, F. High-frequency microrheology reveals cytoskeleton dynamics in living cells. Nat. Phys. 13, 771–775 (2017).
Flaschner, G., Roman, C. I., Strohmeyer, N., Martinez-Martin, D. & Muller, D. J. Rheology of rounded mammalian cells over continuous high-frequencies. Nat. Commun. 12, 2922 (2021).
Moeendarbary, E. et al. The cytoplasm of living cells behaves as a poroelastic material. Nat. Mater. 12, 253–261 (2013).
Bera, K. et al. Extracellular fluid viscosity enhances cell migration and cancer dissemination. Nature 611, 365–373 (2022).
Amitrano, A. et al. Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function. Sci. Adv. 11, eadr5023 (2025).
Katta, S., Krieg, M. & Goodman, M. B. Feeling force: physical and physiological principles enabling sensory mechanotransduction. Annu. Rev. Cell Dev. Biol. 31, 347–371 (2015).
Handler, A. & Ginty, D. D. The mechanosensory neurons of touch and their mechanisms of activation. Nat. Rev. Neurosci. 22, 521–537 (2021).
Kasuba, K. C. et al. Mechanical stimulation and electrophysiological monitoring at subcellular resolution reveals differential mechanosensation of neurons within networks. Nat. Nanotechnol. 19, 825–833 (2024). An integrated multimodal approach enables simultaneous mechanical stimulation and electrophysiological recording of neurons.
Catala-Castro, F. et al. Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology. Nat. Nanotechnol. 20, 411–420 (2025). Time-shared optical tweezer microrheology enables wide-range mechanical mapping of cells and condensates, with applications in ageing and drug screening.
Lukonin, I. et al. Phenotypic landscape of intestinal organoid regeneration. Nature 586, 275–280 (2020).
Gjorevski, N. et al. Tissue geometry drives deterministic organoid patterning. Science 375, eaaw9021 (2022). This paper describes how mechanical patterning can standardize and increase the reproducibility of organoid development.
Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).
Barriga, E. H., Franze, K., Charras, G. & Mayor, R. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo. Nature 554, 523–527 (2018). This seminal work shows that tissue stiffness guides morphogenesis in vivo.
Gjorevski, N. et al. Designer matrices for intestinal stem cell and organoid culture. Nature 539, 560–564 (2016).
Houtekamer, R. M., van der Net, M. C., Maurice, M. M. & Gloerich, M. Mechanical forces directing intestinal form and function. Curr. Biol. 32, R791–R805 (2022).
Nikolaev, M. et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature 585, 574–578 (2020).
Lyu, Q. et al. A soft and ultrasensitive force sensing diaphragm for probing cardiac organoids instantaneously and wirelessly. Nat. Commun. 13, 7259 (2022).
Poling, H. M. et al. Mechanically induced development and maturation of human intestinal organoids in vivo. Nat. Biomed. Eng. 2, 429–442 (2018).
Perez-Gonzalez, C. et al. Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration. Nat. Cell Biol. 23, 745–757 (2021).
Jain, A. et al. Morphodynamics of human early brain organoid development. Nature 644, 1010–1019 (2025). This study represents a technological milestone, enabling long-term, multi-channel imaging of human brain organoids to uncover matrix-dependent morphogenesis.
Schutgens, F. & Clevers, H. Human organoids: tools for understanding biology and treating diseases. Annu. Rev. Pathol. 15, 211–234 (2020).
Kim, J., Koo, B. K. & Knoblich, J. A. Human organoids: model systems for human biology and medicine. Nat. Rev. Mol. Cell Biol. 21, 571–584 (2020).
Garreta, E. et al. Rethinking organoid technology through bioengineering. Nat. Mater. 20, 145–155 (2021).
Wang, X. et al. Anisotropy links cell shapes to tissue flow during convergent extension. Proc. Natl Acad. Sci. USA 117, 13541–13551 (2020).
Jain, A. et al. Regionalized tissue fluidization is required for epithelial gap closure during insect gastrulation. Nat. Commun. 11, 5604 (2020).
Serwane, F. et al. In vivo quantification of spatially varying mechanical properties in developing tissues. Nat. Methods 14, 181–186 (2017).
Grashoff, C. et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263–266 (2010).
Stabley, D. R., Jurchenko, C., Marshall, S. S. & Salaita, K. S. Visualizing mechanical tension across membrane receptors with a fluorescent sensor. Nat. Methods 9, 64–67 (2011).
Ragaller, F. et al. Quantifying fluorescence lifetime responsiveness of environment-sensitive probes for membrane fluidity measurements. J. Phys. Chem. B 128, 2154–2167 (2024).
Casar, J. R. et al. Upconverting microgauges reveal intraluminal force dynamics in vivo. Nature 637, 76–83 (2025). This paper profoundly advanced optical force sensor technology in the infrared regime, enabling non-invasive mechanosensing.
Fardian-Melamed, N. et al. Infrared nanosensors of piconewton to micronewton forces. Nature 637, 70–75 (2025).
Prevedel, R., Diz-Muñoz, A., Ruocco, G. & Antonacci, G. Brillouin microscopy: an emerging tool for mechanobiology. Nat. Methods 16, 969–977 (2019).
Campàs, O., Noordstra, I. & Yap, A. S. Adherens junctions as molecular regulators of emergent tissue mechanics. Nat. Rev. Mol. Cell Biol. 25, 252–269 (2024).
Panciera, T., Azzolin, L., Cordenonsi, M. & Piccolo, S. Mechanobiology of YAP and TAZ in physiology and disease. Nat. Rev. Mol. Cell Biol. 18, 758–770 (2017).
Bock, C. et al. The organoid cell atlas. Nat. Biotechnol. 39, 13–17 (2021).
Wahle, P. et al. Multimodal spatiotemporal phenotyping of human retinal organoid development. Nat. Biotechnol. 41, 1765–1775 (2023).
Mason, J. H. et al. Debiased ambient vibrations optical coherence elastography to profile cell, organoid and tissue mechanical properties. Commun. Biol. 6, 543 (2023).
de Medeiros, G. et al. Multiscale light-sheet organoid imaging framework. Nat. Commun. 13, 4864 (2022).
Tomer, R., Khairy, K., Amat, F. & Keller, P. J. Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy. Nat. Methods 9, 755–763 (2012).
Balzarotti, F. et al. Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes. Science 355, 606–612 (2017).
Chen, W. et al. Live-seq enables temporal transcriptomic recording of single cells. Nature 608, 733–740 (2022).
Otto, O. et al. Real-time deformability cytometry: on-the-fly cell mechanical phenotyping. Nat. Methods 12, 199–202 (2015).
Style, R. W. et al. Traction force microscopy in physics and biology. Soft Matter 10, 4047–4055 (2014).
Elosegui-Artola, A. et al. Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell 171, 1397–1410 (2017).
Ringer, P. et al. Multiplexing molecular tension sensors reveals piconewton force gradient across talin-1. Nat. Methods 14, 1090–1096 (2017).
Sun, X. et al. Mechanosensing through direct binding of tensed F-actin by LIM domains. Dev. Cell 55, 468–482 (2020).
Nava, M. M. et al. Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell 181, 800–817 (2020).
Liu, Y. J. et al. Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells. Cell 160, 659–672 (2015).
Oria, R., Jain, K. & Weaver, V. M. Exploring the intersection of mechanobiology and artificial intelligence. npj Biol. Phys. Mech. 2, 9 (2025).
Oria, R. et al. Force loading explains spatial sensing of ligands by cells. Nature 552, 219–224 (2017).
Lampart, F. L. et al. Morphometry and mechanical instability at the onset of epithelial bladder cancer. Nat. Phys. 21, 279–288 (2025).
Bell, M. K. & Rangamani, P. Design decisions for incorporating spatial and mechanical aspects in models of signaling networks. Curr. Opin. Syst. Biol. 25, 70–77 (2021).
Procopio, A. et al. Combined mechanistic modeling and machine-learning approaches in systems biology – a systematic literature review. Comput. Methods Progr. Biomed. 240, 107681 (2023).
Baker, R. E., Crossley, R. M., Falco, C. & Martina-Perez, S. F. Modelling collective cell migration in a data-rich age: challenges and opportunities for data-driven modelling. Cold Spring Harb. Perspect. Biol. (2026)
Cuomo, S. et al. Scientific machine learning through physics–informed neural networks: where we are and what’s next. J. Sci. Comput. 92, 88 (2022).
Almanstötter, M., Vetter, M. & Iber, D. PINNverse: accurate parameter estimation in differential equations from noisy data with constrained physics-informed neural networks. Preprint at (2025).
Herzog, S. et al. Monitoring the mass, eigenfrequency, and quality factor of mammalian cells. Nat. Commun. 15, 1751 (2024).
Cadoni, S. et al. Ectopic expression of a mechanosensitive channel confers spatiotemporal resolution to ultrasound stimulations of neurons for visual restoration. Nat. Nanotechnol. 18, 667–676 (2023).
Choi, S. H. et al. In vivo magnetogenetics for cell-type-specific targeting and modulation of brain circuits. Nat. Nanotechnol. 19, 1333–1343 (2024).
Kim, Y. J. et al. Magnetoelectric nanodiscs enable wireless transgene-free neuromodulation. Nat. Nanotechnol. 20, 121–131 (2025).
Yang, Q. et al. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. Nat. Cell Biol. 23, 733–744 (2021).