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Scientists have uncovered new details about cellular filaments that play a critical role in wound healing, according to a study in the Proceedings of the National Academy of Sciences.

Vimentin, a protein that forms filaments within cellular cytoskeletons, is critical in helping cells keep their shape and maintain mechanical stability. Additionally, vimentin plays an important role in wound healing and fibrosis. However, the process by which filaments are structured has not been well understood, said Stephen Adam, '86 Ph.D., associate professor of Cell and Developmental Biology, who was a co-author of the study along with Robert Goldman, Ph.D., professor emeritus of Cell and Developmental Biology.

"In previous research, vimentin turned out to have a novel structure that could explain some of its unique physical properties," Adam said. "This provided the impetus to re-investigate vimentin filament assembly which proceeds from a punctate or droplet phase to short filaments and finally, a complete network."

In the study, Adam and his collaborators examined a variant version of vimentin, vimentin-Y117L, which cannot form filaments, and observed that vimentin forms liquid-like droplets.

Investigators also found that the vimentin droplets interacted with actin fibers, another key element of the cytoskeleton.

"Surprisingly, we also found that the droplets coat the actin filaments in the cell in a physical process called wetting and protect the actin filaments from disassembly by actin depolymerizing drugs," Adam said. "We also found that the droplets could move along the actin fibers, sometimes with two droplets fusing together and elongating along the actin."

The findings add to the field's understanding of essential cellular processes, Adam said, and may also be useful in understanding cancer metastasis and other roles for vimentin.

"Vimentin appears to be able to utilize phase separation at all stages of polymer formation, making it a unique cytoskeletal polymer," Adam said. "Other members of the intermediate filament protein family may also be formed by phase separation."

Building on this discovery, Adam and his collaborators will now study the amino acid sequences involved in each stage of filament assembly.

"We would like to know what the structures of the vimentin precursors are inside the droplets and this is being pursued by cryoEM tomography," Adam said. "We are also interested in how post-translational modifications of vimentin, namely phosphorylation, can affect assembly by modifying the phase properties of the protein and the structure of filaments."