Nowadays there are mass photometry techniques that use TIRF-like microscopy technique to measure molecular weight of particles. I wonder if we can derive/deduce molecular weight information directly from cryo-em micrographs as well.
The only thing mass photometry and single-particle cryoEM have in common is that they are single-molecule techniques. They don’t measure the same properties of the molecules.
The best way I can think of to “derive/deduce molecular weight” from cryoEM micrographs is far from direct: obtain a 3D reconstruction of sufficient quality to build a complete atomic model (preferably with an unbiased and automatic method, like ModelAngelo), then from this atomic model you can deduce the sequence and molecular weight. But this is only going to work with ideally-behaved particles, because if you can’t resolve some regions in the 3D reconstruction, you will obtain an incomplete atomic model and will therefore underestimate the molecular weight.
I think these two techniques are best used together. Especially for heterogeneous mixtures, it can be extremely helpful to have a mass photometry measurement: it will tell you how many different species to expect and their relative abundance, which both help a lot to analyze your cryoEM data.