Limits on the accuracy of contact inhibition of locomotion

Cells that collide with each other repolarize away from contact, in a process called contact inhibition of locomotion (CIL). CIL can occur even when cells make micron-scale contact with a neighbor. How precisely can a cell sense cell-cell contact and repolarize in the correct direction? What factors control whether a cell recognizes it has contacted a neighbor? We propose a theoretical model where cells recognize the presence of another cell by binding the protein ephrin with the Eph receptor. This recognition is made difficult by the presence of interfering ligands that bind nonspecifically. Both theoretical predictions and simulations show that it becomes more difficult to sense the contact when it is difficult to distinguish ephrin from the interfering ligands, or when there are more interfering ligands, or when the contact width decreases. However, the error of estimating contact position remains almost constant when the contact width changes because the cell gains spatial information largely from the boundaries of the contact. We then study using statistical decision theory the likelihood of a false positive CIL event and a false negative event. Our results suggest that the cell is more likely to make incorrect decisions when the contact width is very small or so large that it nears the cell's perimeter. In general, we find that cells have the ability to make reasonably reliable CIL decisions even for very narrow contacts, even if the concentration of interfering ligands is ten times that of the correct ligands.