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Is a natural transformation between equivalences necessarily invertible?
No.
For example, when a monoid is regarded as a 1-object category, a natural transformation from its identity functor to itself is the same as an element of the center of the monoid.
For another example, the identity functor from (the category of vector spaces and linear maps) to itself is an equivalence. But there's a natural transformation from this identity functor to itself that sends any vector space to the zero map , and this is not invertible since multiplying by zero is not invertible.
fair enough, endomorphisms save the day again
A friend challenged me to cook up a 2-category with invertible 1- but not 2-cells, hence the question. I couldn't find any such natural transformation, so the example instead was very much similar to John's: take the full subcategory of , at the 1-d vector spaces, deloop it. Now every morphism is invertible, and so is almost every 2-morphism - except for the zero maps.