Characterization of the strain-rate–dependent mechanical response of single cell–cell junctions

Authors

Amir Monemian Esfahani, University of Nebraska-LincolnFollow
Jordan Rosenbohm, University of Nebraska-LincolnFollow
Bahareh Tajvidi Safa, University of Nebraska-LincolnFollow
Nickolay V. Lavrik, Oak Ridge National LaboratoryFollow
Grayson Minnick, University of Nebraska-LincolnFollow
Quan Zhou, Nanyang Technological University, Singapore
Fang Kong, Nanyang Technological University, Singapore
Xiaowei Jin, University of Nebraska-LincolnFollow
Eunju Kim, University of Nebraska-LincolnFollow
Ying Liu, University of Nebraska-Lincoln
Yongfeng Lu, University of Nebraska - LincolnFollow
Jung Yul Lim, University of Nebraska–LincolnFollow
James K. Wahl III, University of Nebraska Medical CenterFollow
Ming Dao, Massachusetts Institute of TechnologyFollow
Changjin Huang, Nanyang Technological University, SingaporeFollow
Ruiguo Yang, University of Nebraska-LincolnFollow

ORCID IDs

Amir Monemian Esfahani https://orcid.org/0000-0003-4800-0467

Bahareh Tajvidi Safa https://orcid.org/0000-0003-1280-5319

Nickolay V. Lavrik https://orcid.org/0000-0002-9543-5634

Grayson Minnick https://orcid.org/0000-0002-6498-7196

Quan Zhou https://orcid.org/0000-0002-1528-7679

Xiaowei Jin https://orcid.org/0000-0002-1034-0477

Yongfeng Lu https://orcid.org/0000-0002-5942-1999

Ming Dao https://orcid.org/0000-0001-5372-385X

Changjin Huang https://orcid.org/0000-0002-1941-1200

Ruiguo Yang https://orcid.org/0000-0002-1361-4277

Document Type

Article

Date of this Version

2-2-2021

Citation

PNAS 2021 Vol. 118 No. 7 e2019347118

https://doi.org/10.1073/pnas.2019347118

Comments

Published under the PNAS license.

Abstract

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