Mechanical & Materials Engineering, Department of


Date of this Version



PNAS 2021 Vol. 118 No. 7 e2019347118


Published under the PNAS license.


Cell–cell adhesions are often subjected to mechanical strains of different rates and magnitudes in normal tissue function. However, the rate-dependent mechanical behavior of individual cell– cell adhesions has not been fully characterized due to the lack of proper experimental techniques and therefore remains elusive. This is particularly true under large strain conditions, which may potentially lead to cell–cell adhesion dissociation and ultimately tissue fracture. In this study, we designed and fabricated a single-cell adhesion micro tensile tester (SCAμTT) using twophoton polymerization and performed displacement-controlled tensile tests of individual pairs of adherent epithelial cells with a mature cell–cell adhesion. Straining the cytoskeleton–cell adhesion complex system reveals a passive shear-thinning viscoelastic behavior and a rate-dependent active stress-relaxation mechanism mediated by cytoskeleton growth. Under low strain rates, stress relaxation mediated by the cytoskeleton can effectively relax junctional stress buildup and prevent adhesion bond rupture. Cadherin bond dissociation also exhibits rate-dependent strengthening, in which increased strain rate results in elevated stress levels at which cadherin bonds fail. This bond dissociation becomes a synchronized catastrophic event that leads to junction fracture at high strain rates. Even at high strain rates, a single cell–cell junction displays a remarkable tensile strength to sustain a strain as much as 200% before complete junction rupture. Collectively, the platform and the biophysical understandings in this study are expected to build a foundation for the mechanistic investigation of the adaptive viscoelasticity of the cell–cell junction.

Supplemental materials & video attached below

Esfahani PNAS 2021 Characterization of the strain-rate SUPPL.pdf (5672 kB)
pnas.2019347118.sm01.mp4 (18521 kB)
Movie S1. Video recordings for the stretch test shown in Figure 3 a-b in the main text

pnas.2019347118.sm02.mp4 (4517 kB)
Movie S2. Video recordings for the stretch test shown in Figure 3 c-d in the main text

pnas.2019347118.sm03.mp4 (2364 kB)
Movie S3. Video recordings for the stretch test shown in Figure 3 e-f in the main text

pnas.2019347118.sm04.mp4 (953 kB)
Movie S4. Video recordings for the stretch test shown in Figure 3 g-h in the main text