Date: Summer 2018
Format: Print / Digital
Skills: 3D, editorial/print design, content development & research
Tools: Cinema4D, Chimera, Adobe Photoshop, Illustrator
Visualizing Bacterial Nano-Machines
Magazine spread breaking down the bacterial
type 4A pilus machine complex
The goal of this project was to visualize a complex biochemical protein, and highlight its structure-function relationships for a graduate BMC course with Dr. Derek Ng. This illustration involved in-depth research into the protein structure and function, as well as the exploration of different visualization methods. I used molecular viewing software Chimera and data from Protein Data Bank. The final illustration was constructed using Cinema4D, Photoshop, and Illustrator.
Date: Summer 2018
Format: Print / Digital
Skills: 3D, print/editorial design, content development & research
Tools: Cinema4D, Chimera. Adobe Photoshop, Illustrator
Visualize a complex biochemical structure, and communicate how its structure relates to its function.
Conception & Background
The “bacterial type 4A pilus machine” is an exciting protein complex whose major structure-function relationships have only recently been revealed. These nano-machines are found in gram-negative bacteria, and are responsible for bacterial movement by acting as a molecular “grappling hooks” for the organism. I chose to depict this protein because I was excited by what other scientists could learn from this research, and its potential application to nano-engineering.
I delved into the research and looked at existing visualizations (below). Although some illustrations of this complex already existed, I felt they didn’t communicate the actual mechanisms behind pilus extension/retraction clearly. The links between structure, function, and movement were not obvious.
Before I began, I decided on three main communication goals to guide my design:
Show the audience which proteins (within the protein complex) drive pilus movement, and how they work.
Show how these key proteins fit together within the overall protein complex.
Design opportunities for interested readers to learn more about other specific proteins within the complex, without overloading them with too much information in one image.
Because the final piece would be done using 3D software (Cinema4D) and real protein data (from the Protein Data Bank), I had a lot of flexibility for how I wanted to communicate the story.
I thought about unique ways to communicate complex structure, and decided that isometric “exploded” views offered some of the best visibility for how objects fit together (these drawing conventions are often used for instruction/assembly manuals). Because the pilus machine was so complex, I wanted to employ a visual method that helped reduce cognitive load while simultaneously allowing viewers to appreciate overall architecture. I audited some manuals, technical specification guides, and assembly instructions for inspiration:
Thumbnails and Rough Concept Sketches
After soliciting feedback from my peers and Professor Ng, I decided that concept sketch #2 (below) best communicated the original three design goals I had in mind. By showing an isometric “exploded” view of this pilus machine, viewers could easily see the overall architecture without being overwhelmed by complexity. Then, the more simplified depiction of pilus machine mechanisms would provide explanation for its structure-function relationship that supplemented the rendered/realistic “exploded” view. Labels within the exploded view provide opportunity for interested researchers to learn more about other specific proteins.
References: 1. Abendroth, J., Murphy, P., Sandkvist, M., Bagdasarian, M., & Hol, W. G. (2005). The X-ray Structure of the Type II Secretion System Complex Formed by the N-terminal Domain of EpsE and the Cytoplasmic Domain of EpsL of Vibrio cholerae. Journal of Molecular Biology,348(4), 845-855. doi:10.1016/j.jmb.2005.02.061. 2. Berry, J., Phelan, M. M., Collins, R. F., Adomavicius, T., Tønjum, T., Frye, S. A., . . . Derrick, J. P. (2012). Structure and Assembly of a Trans-Periplasmic Channel for Type IV Pili in Neisseria meningitidis. PLoS Pathogens,8(9). doi:10.1371/journal.ppat.1002923. 3. Chang, Y., Rettberg, L. A., Treuner-Lange, A., Iwasa, J., Søgaard-Andersen, L., & Jensen, G. J. (2016). Architecture of the type IVa pilus machine. Science,351(6278). doi:10.1126/science.aad2001. 4. Craig, L., Volkmann, N., Arvai, A. S., Pique, M. E., Yeager, M., Egelman, E., & Tainer, J. A. (2006). Type IV Pilus Structure by Cryo-Electron Microscopy and Crystallography: Implications for Pilus Assembly and Functions. Molecular Cell,23(5), 651-662. doi:10.1016/j.molcel.2006.07.004. 5. Hospenthal, M. K., Costa, T. R., & Waksman, G. (2017). A comprehensive guide to pilus biogenesis in Gram-negative bacteria. Nature Reviews Microbiology,15(6), 365-379. doi:10.1038/nrmicro.2017.40.
6. Karuppiah, V., & Derrick, J. P. (2011). Structure of the PilM-PilN Inner Membrane Type IV Pilus Biogenesis Complex from Thermus thermophilus. Journal of Biological Chemistry, 286(27), 24434-24442. doi:10.1074/jbc.m111.243535. Karuppiah, V., Hassan, 7. D., Saleem, M., & Derrick, J. P. (2010). Structure and oligomerization of the PilC type IV pilus biogenesis protein from Thermus thermophilus. Proteins: Structure, Function, and Bioinformatics. doi:10.1002/prot.22720. 8. Leighton, T. L., Dayalani, N., Sampaleanu, L. M., Howell, P. L., & Burrows, L. L. (2015). Novel Role for PilNO in Type IV Pilus Retraction Revealed by Alignment Subcomplex Mutations. Journal of Bacteriology,197(13), 2229-2238. doi:10.1128/jb.00220-15. 8. Lugtenberg, B., & Alphen, L. V. (1983). Molecular architecture and functioning of the outer membrane of Escherichia coli and other gram-negative bacteria. Biochimica Et Biophysica Acta (BBA) - Reviews on Biomembranes,737(1), 51-115. doi:10.1016/0304-4157(83)90014-x. 9. Mccallum, M., Tammam, S., Khan, A., Burrows, L. L., & Howell, P. L. (2017). The molecular mechanism of the type IVa pilus motors. Nature Communications,8, 15091. doi:10.1038/ncomms15091. 10. Misic, A. M., Satyshur, K. A., & Forest, K. T. (2010). P. aeruginosa PilT Structures with and without Nucleotide Reveal a Dynamic Type IV Pilus Retraction Motor. Journal of Molecular Biology,400(5), 1011-1021. doi:10.1016/j.jmb.2010.05.066. 11. Parge, H. E., Forest, K. T., Hickey, M. J., Christensen, D. A., Getzoff, E. D., & Tainer, J. A. (1995). Structure of the fibre-forming protein pilin at 2.6 Å resolution. Nature,378(6552), 32-38. doi:10.1038/378032a0.
12. Sampaleanu, L., Bonanno, J., Ayers, M., Koo, J., Tammam, S., Burley, S., . . . Howell, P. (2009). Periplasmic Domains of Pseudomonas aeruginosa PilN and PilO Form a Stable Heterodimeric Complex. Journal of Molecular Biology,394(1), 143-159. doi:10.1016/j.jmb.2009.09.037. 13. Satyshur, K. A., Worzalla, G. A., Meyer, L. S., Heiniger, E. K., Aukema, K. G., Misic, A. M., & Forest, K. T. (2007). Crystal Structures of the Pilus Retraction Motor PilT Suggest Large Domain Movements and Subunit Cooperation Drive Motility. Structure,15(3), 363-376. doi:10.1016/j.str.2007.01.018. 14. Tammam, S., Sampaleanu, L. M., Koo, J., Sundaram, P., Ayers, M., Chong, P. A., . . . Howell, P. L. (2011). Characterization of the PilN, PilO and PilP type IVa pilus subcomplex. Molecular Microbiology,82(6), 1496-1514. doi:10.1111/j.1365-2958.2011.07903.x. 15. Vollmer, W., & Holtje, J. (2004). The Architecture of the Murein (Peptidoglycan) in Gram-Negative Bacteria: Vertical Scaffold or Horizontal Layer(s)? Journal of Bacteriology,186(18), 5978-5987. doi:10.1128/jb.186.18.5978-5987.2004