Jonah Leher explains the brain's reading pathways and applies this to e-reading:
This research suggests that the act of reading observes a gradient of fluency. Familiar sentences printed in Helvetica activate the ventral route, while difficult prose filled with jargon and fancy words and printed in an illegible font require us to use the slow dorsal route. Here's my rampant speculation (and it's pure speculation because no one has brought a Kindle into a scanner): new reading formats (such as computer screens or E-Books) might initially require a bit more dorsal processing, as our visual cortex adjusts to the image.
(One has to remember that printed books have been evolving to fit the peculiar sensory habits of the brain for hundreds of years - they're a pretty perfect cultural product.) But then, after a few years, the technology is tweaked and our brain adjusts and the new reading format is read with the same ventral fluency as words on a page.
The larger point is that most complaints about E-Books and Kindle apps boil down to a single problem: they don't feel as "effortless" or "automatic" as old-fashioned books. But here's the wonderful thing about the human brain: give it a little time and practice and it can make just about anything automatic. We excel at developing new habits. Before long, digital ink will feel just as easy as actual ink.