title: Spatial distribution of cell-cell and cell-ECM adhesions regulates force balance while main-taining E-cadherin molecular tension in cell pairs.
abstract: Mechanical linkage between cell-cell and cell-extracellular matrix (ECM) adhesions regulates cell shape changes during embryonic development and tissue homoeostasis. We examined how the force balance between cell-cell and cell-ECM adhesions changes with cell spread area and aspect ratio in pairs of MDCK cells. We used ECM micropatterning to drive different cytoskeleton strain energy states and cell-generated traction forces and used a Förster resonance energy transfer tension biosensor to ask whether changes in forces across cell-cell junctions correlated with E-cadherin molecular tension. We found that continuous peripheral ECM adhesions resulted in increased cell-cell and cell-ECM forces with increasing spread area. In contrast, confining ECM adhesions to the distal ends of cell-cell pairs resulted in shorter junction lengths and constant cell-cell forces. Of interest, each cell within a cell pair generated higher strain energies than isolated single cells of the same spread area. Surprisingly, E-cadherin molecular tension remained constant regardless of changes in cell-cell forces and was evenly distributed along cell-cell junctions independent of cell spread area and total traction forces. Taken together, our results showed that cell pairs maintained constant E-cadherin molecular tension and regulated total forces relative to cell spread area and shape but independently of total focal adhesion area.
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Joo Yong
authors.initials: JY
authors.lastname: Sim
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Jens
authors.initials: J
authors.lastname: Moeller
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Hart
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Diego
authors.initials: D
authors.lastname: Ramallo
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Dunn
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305 pruitt@stanford.edu.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Pruitt
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D021982:Cell-Matrix Junctions / Q000502:physiology*; D004285:Dogs; D005109:Extracellular Matrix / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D008954:Models, Biological
chemical_list: D015820:Cadherins