Author interview: Arkaprabha Basu is a postdoctoral fellow in Applied Physics at Harvard University. He obtained his Ph.D. from University of California Los Angeles. His research focuses on the biophysics of the cytoskeleton.
Lab: David A. Weitz, Harvard University
Research Summary: We showed that vimentin can form liquid droplets via liquid-liquid phase separation. These droplets serve as precursors to filaments during their assembly. These droplets coat and wet actin stress fibers.
What was the core problem you aimed to solve with this research?
Vimentin is a type III intermediate filament involved in a broad spectrum of cellular processes such as cancer metastasis and embryonic development. In all such events, the vimentin filament network assembles extremely rapidly; however, comparatively little is known about the actual assembly process. Our goal was to investigate the assembly of vimentin filaments and explore the role of weak, non-specific interactions in the process.
How did you go about solving this problem?
Often in biological research, we ignore the fact that even though proteins and other biomolecules can have specific properties, their overall behavior should be governed by the same laws of physics as non-biological materials. We treated the project as a set of physics questions rather than biology, which allowed us to study the problems from a new perspective. For example, when we observed the vimentin droplets, rather than focusing on their specific composition, we studied whether their behavior and dynamics were similar to traditional liquid droplets.
This is a very exciting and important study. It forces re-examination of how we think about or study proteins and their behavior.
How would you explain your research outcomes (Key findings) to the non-scientific community?
Proteins are traditionally thought of as highly structured biomolecules with very specific binding sites and binding partners. However, in recent years, that proteins, especially unstructured ones interact weakly and non-specifically with one another to form condensates. In this work, we demonstrate that the same proteins can form droplets through weak interactions and form structural filaments. Additionally, these droplets behave exactly how we expect traditional liquid droplets to behave: they merge with one another and wet other surfaces.
What are the potential implications of your findings for the field and society?
Our results have opened a completely new direction for vimentin research as well as cytoskeletal assembly. The fact that a single protein can form liquid droplets as well as filaments is a novel finding. These droplets also exhibit liquid-like properties, such as wetting, which is also an unexplored field for biological condensates. Additionally, wetting of actin stress fibers by these droplets also uncovers a new mode of interaction between the different components of the cytoskeleton.
What was the exciting moment during your research?
The most exciting moment of the research was when we first observed the vimentin structures behave exactly like liquid droplets in the cell using fluorescence microscopy: they merged with one another, split into two, underwent shape fluctuations and wet other structures in the cell.
Reference: Vimentin undergoes liquid–liquid phase separation to form droplets which wet and stabilize actin fibers. https://www.pnas.org/doi/abs/10.1073/pnas.2418624122
