  Cells that collide with each other repolarize away from contact, in a process
called contact inhibition of locomotion (CIL), which is necessary for correct
development of the embryo. CIL can occur even when cells make a micron-scale
contact with a neighbor - much smaller than their size. 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 for the limits of CIL 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 simulation results show
that it becomes more difficult to sense cell-cell 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. This happens because the cell gains spatial information largely from
the boundaries of cell-cell contact. We study using statistical decision theory
the likelihood of a false positive CIL event in the absence of cell-cell
contact, and the likelihood of a false negative where CIL does not occur when
another cell is present. 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. However, in general, we find that cells have the
ability to make reasonably reliable CIL decisions even for very narrow
(micron-scale) contacts, even if the concentration of interfering ligands is
ten times that of the correct ligands.
