by Christoph
Figure 1. Cryo-ET image of an ultra-small bacterial cell. The cell has a very dense interior compartment and a complex cell wall. The darker spots at each end of the cell are most likely ribosomes. The image was obtained from a 3-D reconstruction. Scale bar: 100 nm. Credit: Berkeley Lab. Source. Frontispiece: Detail from a Mycoplasma cell. By Martina Maritan. Source
Our ability to visually perceive and discriminate is always slighly overwhelmed by black-and-white images. Especially, of course, when the objects depicted are outside our trained, familiar size spectrum, such as bacterial cells and their innards. Take for example Figure 1, the cryo-ET image of a tiny bacterial cell (Scale bar: 100 nm!) that I had shown here before. It doesn't take much practice and only a few credible hints to "see" the cell wall, the ribosomes, and the very compact nucleoid. But that's about it.
Could you "see" a cell's innards in a color image better? Sadly, the cytoplasmic cell components are not inherently colorful, that is, they mostly do not absorb light in the visible spectrum (which would not be of much use in electron microscopy anyway). Biology textbooks usually get around this problem by resorting to colored schematic diagrams, here's the Wikipedia version. But David Goodsell from The Scripps Research Institute, La Jolla CA has gone a different way: drawing and coloring a cell with all its macromolecular components from scratch.
Figure 2. Detail from a Mycoplasma cell, partiallly "peeled" by removing macromolecule levels. By Martina Maritan (modified). Source
Already in 1999, for his first version of an E. coli cell, a part of it, he made three important decisions: 1. individual classes of macromolecules get their own, easily recognizable color; 2. all macromolecules are shown in their relative sizes/shapes, and allowing for their rotation in space and including their interactions, for example, ribosomes with tRNA and mRNA; 3. all macromolecules are shown in their approximate cellular concentrations. The third point in particular gives you a vivid impression of what cell biologists call "macromolecular crowding". But keep in mind that water molecules and ions ─ the broth of the cytoplasmic soup ─ are still 2−3 orders of magnitude smaller, and intentionally not shown to prevent any hallucinogenic effects.
Concerning the colors, I always had the impression that David was inspired for his specific palette by the animated movie Yellow Submarine by The Beatles (he didn't confirm it yet). Concerning the sizes and shapes of the depicted macromolecules, he now relies mostly on the structural data deposited in the Protein Data Bank (PDB); see the now even more detailed E. coli cell in the 2021 version. PDB is such a useful "public library" that not only can David borrow the "books" he needs there, but also electron microscopists borrow "books" there as templates for detecting and "coloring" structures in their cryo-tomograms (see Figure 3 in this STC post.)
Figure 3. Detail from a Mycoplasma cell. Yellow: chrDNA, magenta: ribosome, pink: tRNA, salmon: mRNA, orange: translation factors and RNA polymerase, bue hues: proteins.By Martina Maritan. Source
Now, David and his team have gone one step further by Building Structural Models of a Whole Mycoplasma Cell. Figure 2 is a screenshot from their movie worth watching repeatedly, and Maritan et al. (2022) say on the dedicated website:"This snapshot represents a Mycoplasma cell at the beginning of its life cycle. Cell shape has been approximated to a sphere with a radius of ~145 nm. Each protein is represented by a 3D structure coming from either homology modeling, a previous model of mycoplasma cytoplasm, experimental data, or homologues from the Protein Data Bank. The nucleoid structure was modeled with LatticeNucleoid [software]. Small molecules, ions, and water are not shown in the illustrations, and would fill the spaces between the macromolecules. Different clipping planes and coloring schemes have been applied to the model to highlight specific areas/elements of the cell." Teachers among our readers may want to study the computational route for obtaining this cell model in more detail here. I wish that this model of a prokaryotic cell will soon replace all these, well, nonsensical diagrams in textbooks and perhaps work against the widespread opinion that bacterial cells are "simple".
Another piece of work from David Goodsells workshop, the Mycoplasma JCVI-syn3A minimal cell in the process of division, was recently featured in The New Yorker, with the title A Journey to the Center of Our Cells. A warmly recommended reading, but don't take the "our" in the title too literally. Bacterial cells are not insignificantly different from eukaryotic cells like ours (which should have gotten around to The New Yorker by now).
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