The matrix reveals nanoscale patterns in the model organism

Species throughout the animal kingdom have important interfaces between the outer layers of their bodies and the environment. Complex microstructures—featured in the outer skin layers of humans, for example—are known to assemble into matrix formations.

But how these complex structures, known as apical extracellular matrices (aECMs), are integrated into elaborately woven structures remains an elusive question.

Now, following years of research and the power of technologically advanced instrumentation, University of California San Diego scientists have unraveled the underpinnings of such matrices in a tiny nematode. The roundworm Caenorhabditis elegans has been studied extensively for decades because of its transparent structure, which allows researchers to peer inside its body and examine its skin.

As described in the journal Nature Communications, School of Biological Sciences researchers now understand the assembly of AECM patterns in nanoscale roundworms. A powerful, super-resolution microscope helped reveal previously unseen structures related to columns called struts, which are key to the proper growth and function of aECMs.

„Struts are like little pillars that connect different layers of the matrix and act as a kind of scaffolding,” said Andrew Chisholm, a professor in the School of Biological Sciences and senior author of the paper.

Although roundworms serve as model organisms for laboratory studies because of their simple, transparent bodies, they have complex structures beneath the surface. They contain nearly 20,000 genes, not unlike the number of human genomes, and provide lessons about the structure and function of more advanced organisms.

By focusing on the roundworm exoskeleton, called the cuticle, the researchers found that defects in the struts caused unnatural layer swelling, or „blisters.” Within the cuticle layer, research studies focus on collagens, which are the most abundant family of proteins in our bodies and help hold body materials together.

„Struts hold critical layers together,” Chisholm said. „Without them, the layers separate, causing blister-like disorders. You don’t see any struts in blister mutants.”

Conventional laboratory equipment previously imaged struts without detail, often resulting in ill-defined bubbles. But through the lab of Andreas Ernst, assistant professor of biological sciences, they had access to advanced tools — known as 3D-structured illumination super-resolution microscopy (3D-SIM) — that allowed the struts to come into stunning focus and define their functions more easily. The researchers were then able to resolve the nanoscale structure of the struts and the previously undocumented design of the shear layer.

„We were able to see exactly where these proteins go in the matrix,” Chisholm said. „It’s a paradigm of how the matrix can assemble into very complex structures and very complex patterns.”

The two first authors, Jennifer Adams (Senior Research Associate) and Murugesan Pooranachitra (Master’s), contributed equally to the article. Other co-authors are Erin Jiao, Sherry Li Zheng, Alexander Goncharov, Jennifer Crew, James Kramer, neurobiology professor Yishi Jin, assistant professor of cell and developmental biology Andreas Ernst and Andrew Chisholm.

Sherry Zheng was a UC San Diego Triton Research and Experiential Learning Scholar and recipient of the Gabriel Wienhausen Biological Sciences Scholarship.