Cadherin-dependent mechanotransduction depends on ligand identity but not affinity.
This study investigates the relationship between classical cadherin binding affinities and mechanotransduction through cadherin-mediated adhesions. The mechanical properties of cadherin-dependent intercellular junctions are generally attributed to differences in the binding affinities of classical cadherin subtypes that contribute to cohesive energies between cells. However, cell mechanics and mechanotransduction may also regulate intercellular contacts. We used micropipette measurements to quantify the two-dimensional affinities of cadherins at the cell surface, and two complementary mechanical measurements to assess ligand-dependent mechanotransduction through cadherin adhesions. At the cell surface, the classical cadherins investigated in this study form both homophilic and heterophilic bonds with two-dimensional affinities that differ by less than threefold. In contrast, mechanotransduction through cadherin adhesions is strongly ligand dependent such that homophilic, but not heterophilic ligation mediates mechanotransduction, independent of the cadherin binding affinity. These findings suggest that ligand-selective mechanotransduction may supersede differences in cadherin binding affinities in regulating intercellular contacts.
Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, IL 61801, USA.
Hamid
H
Tabdili
Matthew
M
Langer
Quanming
Q
Shi
Yeh-Chuin
YC
Poh
Ning
N
Wang
Deborah
D
Leckband
D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002452:Cell Count; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D008024:Ligands; D040542:Mechanotransduction, Cellular; D017711:Nonlinear Dynamics; D051419:Paxillin / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D000199:Actins; D015820:Cadherins; D008024:Ligands; D051419:Paxillin