Lyse your cells in 100% formic acid to get 40% more membrane proteins??

Okay. Chemically I do not understand why this would work. That's okay, I don't understand how a lot of things work....

They start out by laser capture microdissecting a pretty big area of cells. Something like 500 micron x 500 in 15 micron cuts. And you stop wondering why the cut is that big when you see the digests are loaded on a Q Exactive Classic. Man, I love those old things, but proteomics has moved forward a good bit since 2012. 

They seriously just put 5 microliters of 100% formic acid onto the slices and dry it off by speedvac and then LysC digest for 3 hours and then trypsin digest overnight. Big boost in membrane protein IDs over just DDM lysis alone.

Then they repeat it with smaller sections using an Astral. There might be two rounds of this to get to very small cuts. This ends up letting them see everyone's least favorite super important proteins, those awful SLC things. And it isn't a small list. They pick up several of them. 

If you are also struggling with low input preps under-representing membrane proteins, this might be worth checking out. I suspect you probably have LCMS grade formic acid sitting around somewhere.