Diogo Melo’s post

Last post we talked about how we could go from a protein crystal to a structure (Fig. 1 shows the protein crystal size). But what about the protein crystal itself? Getting the protein crystals formed in the first place is often a major bottle neck in this field of research. I thought: scientists struggle a great deal in this procedure, why wouldn’t I share the burden with you? So off we go to see how protein crystals are made.

  • What are crystals in the first place?

In order to understand how the protein crystals are made, we need to understand what crystals are at the molecular level. We can say an object is crystalline if the atoms or molecules within it are organized, i.e. they are periodic. In other words, you could take a fragment of the total crystal (the unit cell), copy it in different directions and you would get again the original (like copying a single square in Fig. 1.e – this is a simplistic way of visual representation; they are not really packed like that).

Figure 1: (a) I am holding a magnetic wand (sadly not as multi-functional as Harry Potter’s). On the end of the wand is a “loop” (b) I’ve zoomed in a bit here to show you the loop holder but the loop itself can only be clearly seen under a microscope (c). I use loops of various styles and sizes loops are used to “fish” my protein crystals (d) out of the solution they grow in. Protein crystals are made of billions of proteins arranged in an orderly fashion (e) each protein makes contact (direct or indirect) with its neighbours, sustaining this way the crystal form itself.

Since a crystal is formed from many copies of a unit cell, its properties will also drastically change with a significant change in unit cell itself. Let’s compare a diamond crystal, with a water crystal (ice), and a protein crystal:

– Diamonds are crystals of carbon atoms chemically bound to each other. The individual chemical bonds are strong and hard to break, which is why diamond itself is also so strong and hard to break.

– Ice is made of water molecules. These are not chemically bond (non-covalent), but do still interacting with each other. These weak interactions are much easier to break than diamond’s chemical bonds, but there are lots of them. Therefore ice cubes are still fairly rigid and hard, although they are softer than diamonds.

– Protein crystals are softest in the group. Compared to water molecules (3 atoms), proteins are absolutely huge molecules (1000s atoms), which in crystal form interact with one another with a diverse array of weak interactions. In addition, proteins are lumpy and so they don’t pack together very well. The gaps between individual protein molecules are filled with liquid. This means they are more like a cube of jello than a diamond or ice crystal.  


Figure 2: If I google “lattice steel crane”, “lattice wood crane”, and “lattice paper crane” I get the corresponding first hits. How much weight do you think each can take? This serves as an analogy for how hard diamond, ice and protein crystals are when compared to each other. Sadly, a protein crystal is not as easy to produce as a paper crane… Google search at 13/05/2019

To visualize how resistant to physical stress a protein crystal is, we can imagine that if the diamond crystal structure is like a steel lattice crane (metal components fused together), ice would be like a wooden crane (wood components fitted together) and a protein protein crystal would be a paper crane (is there even such a thing? Check Fig 2). Note this is a very rude analogy, think of it only in terms of how strong each one is and how much weight can it sustain before deforming.

There are many different naturally occurring crystals on earth, each one’s characteristics depend on their chemical composition, molecular arrangement and interactions. Small changes to the crystals’ composing molecules can drastically change the crystal itself (remember, that the crystal is made many of the same molecules arranged together in an organized fashion). Some crystals like in “Cueva de los Cristales” can even be larger than 10 meters in length!