Cells become noninteractive when new requests are added to the matrix with popup open
When new requests are caught and added to the matrix you are not able to make any changes to the matrix (or a cell, rather) unless you mouse over some other cell or reopen the popup.
A good place to test is on any YouTube video, where lots of new requests are made when watching a video. But it can also happen when you reload a page within the popup and more requests are caught.
This has been the case since HTTPSB: when the matrix refreshes, the hotspots are removed from the cell under the mouse, so we need to move the mouse pointer again for the hotspots to be re-inserted in the cell.
I could probably remember the specific cell hostname/type into which the hotspots are installed before updating the matrix, and re-install them.
Somehow I never noticed this in HTTPSB.