Implications of using a USB SSD drive to run VM images off
USB 3.0 supports UASP which allows for TRIM

Re: enclosures - If you're using an external enclosure, the chipset must be able to pass through TRIM commands to the drive.  So without that, everything is a moot point.  And when connected in this manner, I would venture the drive would probably not even be recognized by the system as an SSD.

Question - can't you just upgrade your internal SSD to a larger capacity?