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Since you are already using a signature verification method on the file itself, just modify that system a little bit: Sign individual chunks of the file, and store the signatures inline. If your signature takes 32 bytes, and you use a 4,096 byte chunk size, you can have 4,064 bytes data + 32 bytes signature in each chunk. Sign the list of signatures, and ...
I haven't tried this, but I know there are APIs for file change notification: ReadDirectoryChangesW for Windows (Archived here.) FSEvents for Mac OS X
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