From large, perfect crystals to atomic structures from grains of dust - how crystallography revolutionized medicine and our understanding of matter
Explore the TransformationOnce the domain of large, perfect crystals and photographic film, crystallography has transformed into a field that can decipher atomic structures from grains of dust, revolutionizing how we design medicine and understand the building blocks of life 8 .
For over a century, it has been one of the most important techniques for understanding the world around us, from why diamonds are hard and shiny to how our immune system fights off viruses 5 . The field is far from static; it is undergoing a radical transformation, pushing into new frontiers and revealing secrets of matter that were once thought to be beyond its reach.
At its heart, crystallography relies on a simple principle: a crystalline material consists of a regular, repeating arrangement of atoms in three-dimensional space 1 . This repetitive structure is the key to unlocking its secrets.
The infinite repeating pattern of a crystal is called the crystal lattice. The smallest repeating unit within this lattice is the unit cell, a parallelepiped characterized by its edge lengths (a, b, c) and the angles between them (α, β, γ) 1 . The specific arrangement of atoms repeated at each point of the lattice is known as the motif 1 .
The relationship between atoms, unit cells, and crystal lattices forms the foundation of crystallographic analysis.
Crystals are classified by their symmetry. These symmetries group all possible crystals into seven crystal systems, each with a unique set of characteristics for its unit cell 1 . The fourteen Bravais lattices further define the distinct ways points can be arranged in space to satisfy these symmetries 1 .
| Crystal System | Defining Symmetry | Unit Cell Characteristics | Example |
|---|---|---|---|
| Triclinic | One-fold axis | a ≠ b ≠ c; α ≠ β ≠ γ | Plagioclase Feldspar |
| Monoclinic | Two-fold axis | a ≠ b ≠ c; α = γ = 90°, β > 90° | Clinopyroxenes |
| Orthorhombic | Three perpendicular two-fold axes | a ≠ b ≠ c; α = β = γ = 90° | Olivine |
| Tetragonal | Four-fold axis | a = b ≠ c; α = β = γ = 90° | Leucite |
| Trigonal | Three-fold axis | a = b = c; α = β = γ < 120°, ≠ 90° | Ilmenite, Quartz |
| Hexagonal | Six-fold axis | a = b ≠ c; α = β = 90°, γ = 120° | Magnesium, Apatite |
| Cubic | Four three-fold axes (parallel to <111>) | a = b = c; α = β = γ = 90° | Diamond, Table Salt |
The story of crystallography is one of constant evolution, driven by the need to see more and see smaller.
The story of modern crystallography began in 1912 when German physicist Max von Laue and colleagues discovered that X-rays diffracted when passed through a crystal, proving both the wave-like nature of X-rays and the periodic lattice structure of crystals 5 . The following year, father and son team William Henry Bragg and William Lawrence Bragg built on this discovery. They showed that the diffraction patterns could be used to determine the precise positions of atoms within a crystal, famously demonstrating this by working out the three-dimensional structure of a diamond 5 . This breakthrough, which earned them a Nobel Prize, made X-ray crystallography the definitive technique for determining atomic structure.
A major limitation of traditional X-ray crystallography is the need for relatively large, high-quality single crystals. For many materials, particularly biological molecules and complex natural products, growing such crystals is impossible 6 . This long-standing obstacle is now crumbling. Recent advancements have introduced powerful new strategies:
This technique leverages the wave-particle duality of electrons. It allows researchers to perform single-crystal diffraction on samples smaller than those at the limit of X-ray diffraction—sometimes as small as a few hundred nanometers or less 8 6 . This has opened the door to determining structures from powders and nanocrystals that were previously intractable 2 .
This innovative approach bypasses crystal growth altogether. A pre-prepared porous crystal acts as a host, absorbing guest molecules (the sample of interest) into its pores. The structure of the guest molecule can then be determined by analyzing the host-guest complex 6 .
| Technique | Core Principle | Best For | Key Advantage |
|---|---|---|---|
| MicroED | Electron diffraction on nanocrystals | Proteins, natural products, materials that form micro-crystals | Determines 3D structures from crystals too small for X-rays 8 6 |
| Crystalline Sponge | Absorbing sample molecules into a porous host crystal | Molecules that are difficult or impossible to crystallize | Eliminates the need to grow a single crystal of the target molecule 6 |
| Synchrotron Crystallography | Using extremely intense X-rays from a particle accelerator | Complex structures like viruses, large proteins | High-intensity beam allows for shorter exposures and higher-quality data 3 5 |
To understand how crystallography works in practice, let's walk through the steps of a classic protein structure determination, a process that has shed light on the mechanisms of life and the design of countless drugs 3 .
The first and often most difficult step is to obtain a purified, concentrated sample of the protein. This solution is then subjected to crystallization trials, where conditions are meticulously varied to slowly coax the protein out of solution and form an ordered crystal 3 .
The frozen crystal is mounted on a goniometer, which precisely rotates it in the path of a monochromatic X-ray beam. As the crystal rotates, the X-rays diffract off the atomic planes within the lattice 3 .
The final output of this painstaking process is a precise, three-dimensional atomic model of the protein. This is not just a static picture; it reveals how the protein functions. For example, by studying the structure of an enzyme, scientists can identify the active site where a chemical reaction occurs. In drug discovery, the structure of a viral protein can be used to design a small molecule that fits perfectly into a pocket, blocking the virus's activity. This "structure-based drug design" is a direct application of crystallography that has revolutionized medicine 3 .
The changing face of crystallography is not just about smaller samples; it's about integration and new applications. NMR crystallography is now used to study materials that are not perfectly ordered, bridging the gap between crystalline and amorphous states 9 . In materials science, crystallography is used to engineer the crystal orientation in lithium-ion battery cathodes, designing materials with optimal pathways for lithium ions to improve battery performance and safety 9 .