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The interplay between cell-cell and cell-substrate interactions is complex yet necessary for the formation and well-functioning of tissues. The same mechanosensing mechanisms used by the cell to sense its extracellular matrix, also play a role in intercellular interactions. We used the discrete element method to develop a computational model of a deformable cell that includes subcellular components responsible for mechanosensing. We modeled a cell pair in 3D on a patterned substrate, a simple laboratory setup to study intercellular interactions. We explicitly modeled focal adhesions between the cells and the substrate, and adherens junctions between cells. These mechanosensing adhesions matured; their disassembly rate was dictated by the force they carry. We also modeled stress fibers which bind the discrete adhesions and contract. The mechanosensing fibers strengthened upon stalling and exerted higher forces. Traction exerted on the substrate was used to generate maps displaying the magnitude of the tractions along the cell-substrate interface. Simulated traction maps are compared to experimental maps obtained via traction force microscopy. The model recreates the dependence on substrate stiffness of the tractions’ spatial distribution across the cell-substrate interface, the contractile moment of the cell pair, the intercellular force, and the number of focal adhesions. It also recreates the phenomenon of cell decoupling, in which cells exert forces separately when substrate stiffness increases. More importantly, the model provides viable molecular explanations for decoupling. It shows that the implemented mechanosensing mechanisms are responsible for competition between different fiber-adhesion configurations present in the cell pair. The point at which an increasing substrate stiffness becomes as high as that of the cell-cell interface is the tipping point at which configurations that favor cell-substrate adhesion dominate over those favoring cell-cell adhesion. This competition is responsible for decoupling. Additionally, we learn that extent of decoupling is modulated by adherens junction maturation.Statement of SignificanceCells are sensitive to mechanical factors of their extracellular matrix while simultaneously in contact with other cells. This creates complex intercellular interactions that depend on substrate stiffness and play a role in processes such as development and diseases like cardiac arrhythmia, asthma, and cancer. The simplest cell collective system in vitro is a cell pair on a patterned substrate. We developed a computational model of this system which explains the role of molecular adhesions and contractile fibers in the dynamics of cell-cell interactions on substrates with different stiffness. It is one of the first models of a deformable cell collective based on mechanical principles. It recreates cellular decoupling, a phenomenon in which cells exert forces separately, when substrate stiffness increases.

This study was designed to gain insight into the influence of the attachment system on the loading conditions of oral implants supporting a mandibular overdenture on two implants. Five patients were selected and were provided with two implants in the canine area of the mandible (Branemark System). All patients received a new mandibular overdenture that could be mounted on an ovoid-shaped bar (Dolder, C&M): (a) with and (b) without bilateral extensions and (c) on ball-attachments (Nobel Biocare). Using three strain gauges attached to the outer surface of the 5.5-mm standard abutments, the axial forces and bending moments on both supporting implants could be quantified. Load registrations were made during application of 50 N on seven predetermined positions along the occlusal surface of the prosthesis and during maximal biting in maximal occlusion (clenching). The results revealed no differences in induced axial force for the various anchorage devices, unlike the differences in bending moment. Although there is a tendency for better axial load sharing with bars and better sharing of bending moments with ball attachments, these differences were not significant.