Judging by how big of a feat this is to image a molecule, how on earth do we know how things like cellular respiration work? How do we know cells use ATP, etc without being able to watch?
(I may make this question a separate post to HN, it's been bothering me for a while.)
Biochemists use easily hundreds of different techniques to elucidate, logically or probabilistically, details about cellular processes. They take serious advantage of techniques like optical properties of solutions and selective targeting of fluorescent tags to visualize effects. Moreover, they tend to abuse the very nanomachine proteins they're trying to study in order to study them further.
A simple example (the names are removed to make this easier to digest, but if you're curious it's the action of Glyceraldehyde-3-Phosphate Dehydrogenase in glycolysis) involves a protein which is known to play a part in the breakdown of glucose. This protein catalyzes the addition of a "high energy" phosphate to our compound so we can break it down further while also pulling off a reactive hydrogen (and adding it to NAD+ to make NADH) so the cell can use that later (another kind of energy like ATP).
Biochemists, assuming they can already purify the compound and know the overall reaction, investigated the action of the enzyme by mixing in a highly reactive fluorescent-tagged molecule that looks similar to the product of the reaction. This molecule bound permanently to the inside of the enzyme which was then denatured and sequenced, looking for whatever amino acid showed the fluorescent tag (cysteine). Then the inserted modified reagents which contained radioactive hydrogen and phosphate to figure out where exactly those molecules ended up. In this way they learned where the enzyme added the phosphate to the product and exactly which hydrogen was removed from the initial compound to make that NADH.
Biochemistry is a really fascinating story of minute triumphs of discovery. Unfortunately, like any part of science like that, it means that the day-to-day life of a biochemist is backbreaking and tedious. Regardless, if you're interesting, there is a lot of fun stuff to study.
Not a biologist, but I've been in bio labs and it is _meticulous_ work. Very, very clever processes for detecting molecules as they pass through (or don't pass through) certain organelles, a good dose of math, some inference, and sometimes luck.
Not being able to see (and as the toothpick -> truck of floss poster mentioned above, this isn't going to help with biological systems much at this point) does mean there are significant gaps in what biologists know. On the other hand, biologists have been visualizing larger structures for some time (even proteins via xray etc.)
(I may make this question a separate post to HN, it's been bothering me for a while.)