Scientists reveal hidden dynamics of the cell’s smallest structures

Scientists at Feinberg are reshaping scientific understanding of the cell’s tiniest components—structures once thought to be static, now revealed to be dynamic engines of cellular life. As they probe the inner workings of cells, they are not only expanding understanding of cellular processes but also paving the way for novel therapies and diagnostics.

Recent research led by Vladimir Gelfand, Ph.D., the Leslie B. Arey Professor of Cell, Molecular, and Anatomical Sciences, and Sergey Troyanovsky, Ph.D., professor of Dermatology, and of Cell and Developmental Biology, has illuminated new roles for cytoskeletal filaments and intercellular junctions, while a separate study by Brian Mitchell, Ph.D., associate professor of Cell and Developmental Biology, has identified a novel mechanism that protects epithelial cells from damage.

How cells generate motion

In a study published in the Journal of Cell Biology, Gelfand’s team used advanced imaging techniques to observe vimentin intermediate filaments—key components of the cytoskeleton—within living cells.

“Essentially, these filaments are typically considered as the most non-dynamic component of the cytoskeleton,” Gelfand said. “People generally believe that filaments just help cells to keep their shape and prevent mechanical damage. But a long time ago, we started to suspect that the filaments are more dynamic than people think.”

Contrary to long-held beliefs that these filaments are rigid and bundled, Gelfand and his laboratory found that vimentin filaments are highly mobile and travel individually along microtubules, the cell’s internal highways. This discovery redefines the role of intermediate filaments, suggesting they actively participate in intracellular transport and structural adaptation.

“There are multiple of these microtubules forced by the molecular motors and they hydrodynamically interact with each other,” said Sayantan Dutta, Ph.D., a visiting scientist at Feinberg and former student at Princeton and the Flatiron Institute’s Center of Computational Biology, who was first author of the study.

“Due to the hydrodynamic interaction, the microtubules bend in a coordinated fashion to create a large-scale flow. That’s our main discovery that is supported both by extensive computer simulations and also by the supplemental imaging.”

In another study published in Nature Physics, Gelfand and colleagues discovered that the cytoplasm within cells is far from inert. Instead, it’s stirred by microscopic “twisters”—vortex-like movements that help distribute organelles and other cellular cargo. These swirling motions, observed in oocytes (immature egg cells), are driven by the cytoskeleton, a network of protein filaments that acts like scaffolding and a transport system. The findings suggest that cytoplasmic organization is a highly orchestrated process, essential for proper cell development and function.

What holds cells together

Troyanovsky’s research focused on adherens junctions, the protein complexes that hold cells together. In a study published in Nature Communications, his team uncovered new insights into how intercellular “glue” functions to enable interactions between cells.

“What we have studied here, in simple words, is the glue that connects cells,” said Troyanovsky. “One of the basic questions here was: ‘What’s first? The two cells make contact and then intracellular machinery responds, or vice versa?”

In the study, his team revealed that these junctions form through a stepwise process, beginning with tiny “pre-junctions” that eventually mature into full adhesive structures. This insight into cellular adhesion could have implications for understanding tissue development and diseases like cancer and eczema, he said.

Adding another layer to this cellular narrative, Brian Mitchell’s lab discovered a previously unknown mechanism that epithelial cells use to cope with overcrowding—a common stressor in tissue environments. Instead of undergoing cell extrusion, which can be damaging, epithelial cells initiate macropinocytosis—a process in which the cell engulfs extracellular material. This action shrinks the apical surface of the cell, relieving pressure and preserving tissue integrity.

How cells respond to crowding

“As tissue gets crowded, these events happen periodically to stop them from needing to go through this cell extrusion process. Both of these processes can solve the problem, but cell extrusion is more costly and non-reversible,” Mitchell said.

The study, published in Nature Communications, was conducted in frog embryos and identifies one way that cells adapt to mechanical stress without sacrificing their own viability.

Together, these studies underscore a paradigm shift in cell biology: the smallest structures within cells are not passive scaffolds, but active participants in maintaining cellular health, communication and adaptability.

As Feinberg scientists continue to explore these microscopic mechanisms, their work promises to inform new therapeutic strategies and deepen the understanding of life at its most fundamental level.