Deletion of the cytoplasmic domain of N-cadherin reduces, but does not eliminate, traction force-transmission.
Collective migration of epithelial cells is an integral part of embryonic development, wound healing, tissue renewal and carcinoma invasion. While previous studies have focused on cell-extracellular matrix adhesion as a site of migration-driving, traction force-transmission, cadherin mediated cell-cell adhesion is also capable of force-transmission. Using a soft elastomer coated with purified N-cadherin as a substrate and a Hepatocyte Growth Factor-treated, transformed MDCK epithelial cell line as a model system, we quantified traction transmitted by N-cadherin-mediated contacts. On a substrate coated with purified extracellular domain of N-cadherin, cell surface N-cadherin proteins arranged into puncta. N-cadherin mutants (either the cytoplasmic deletion or actin-binding domain chimera), however, failed to assemble into puncta, suggesting the assembly of focal adhesion like puncta requires the cytoplasmic domain of N-cadherin. Furthermore, the cytoplasmic domain deleted N-cadherin expressing cells exerted lower traction stress than the full-length or the actin binding domain chimeric N-cadherin. Our data demonstrate that N-cadherin junctions exert significant traction stress that requires the cytoplasmic domain of N-cadherin, but the loss of the cytoplasmic domain does not completely eliminate traction force transmission.
Biomedical Engineering Department, University of California, Davis, United States.
Eliot
E
Lee
Biomedical Engineering Department, University of California, Davis, United States.
Makena L
ML
Ewald
Biomedical Engineering Department, University of California, Davis, United States.
Mary
M
Sedarous
Biomedical Engineering Department, University of California, Davis, United States.
Timothy
T
Kim
Biomedical Engineering Department, University of California, Davis, United States.
Brent W
BW
Weyers
Biomedical Engineering Department, University of California, Davis, United States.
Rose Hong
RH
Truong
Biomedical Engineering Department, University of California, Davis, United States. Electronic address: syamada@ucdavis.edu.
Soichiro
S
Yamada
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004285:Dogs; D020724:Elastomers / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D061985:Madin Darby Canine Kidney Cells; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D018613:Microscopy, Confocal; D009154:Mutation; D013314:Stress, Mechanical; D013499:Surface Properties; D059008:Time-Lapse Imaging / Q000379:methods
D015820:Cadherins; D020724:Elastomers; D005353:Fibronectins; D017228:Hepatocyte Growth Factor
Actin cytoskeleton; Collective cell migration; Hepatocyte Growth Factor; MDCK; N-cadherin; Traction force