Watch these cells rapidly create protrusions for exploration and movement

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In order to move, cells must be able to rapidly change shape. A team of researchers from the University of North Carolina at Chapel Hill show that cells achieve this by storing extra “skin” in folds and bumps on their surface. This cell surface excess can be rapidly deployed to cover temporary protrusions and then folded away for next time. The study appears May 17 in the Biophysical Journal.

Cell membranes are very flexible, but they can only stretch by approximately 3% without rupturing. Having extra wrinkles of surface area that can expand on demand allows cells to move and divide while safely maintaining cell volume and membrane integrity.

“It’s a safety measure because you can’t stretch the cell membrane, and if it breaks, the cell will lyse and die, so cells need to have this reserve,” says first author Maryna Kapustina, a biophysicist at the University of North Carolina at Chapel Hill. “These projections can store massive amounts of cell surface and are highly dynamic, which means they can be rapidly dismounted and immediately rebuilt in other locations on the cell periphery.”

Cell surface protrusions came in various shapes and sizes. Some, called blebs, are small, rounded bumps on the cell surface with very little internal structure. Blebs form within seconds and shrink after several minutes. Larger locomotory protrusions take longer to form but can last for more than an hour thanks to their supportive internal structure, which is made of proteins such as microtubules and actin.

The researchers used electron and fluorescence microscopy to observe rounded, cigar-shaped, and irregularly shaped cells that were embedded in a 3D collagen matrix, a meshwork of collagen fibers that the cells could squeeze and migrate through. They used fluorescent tags to capture time-lapses of the cells’ surface dynamics and locomotion over the course of several hours.

The team showed that when the cells were rounded, their surfaces were rough and complex; covered with numerous tiny surface projections such as blebs, microvilli, filopodia, and folds. However, when the cells extended protrusions, these extra wrinkles of “skin” unfolded and their surfaces became relatively smooth, especially in the regions adjacent to the protrusions.

The researchers think that cell surface excess is important during both mesenchymal and ameboid locomotion, the two main ways that cells move. During mesenchymal locomotion, cells adhere to surfaces in their environment and then use contractile forces to push itself between the collagen fibers or crawl along 2D surfaces. During ameboid locomotion — which allows for much faster movement — cells don’t rely on adhesions but are instead propelled by the rapid movements of smaller “blebby” protrusions.

The team thinks that microtubules play an important role in regulating cell surface excess during both mesenchymal and ameboid locomotion, though their exact function is unclear. “Microtubules might be providing mechanical support for the cell surface, or it might have something to with activating actin beneath the cell membrane to create an active site for a stable protrusion,” says Kapustina. “When you don’t have this active site to create a stable protrusion, the cells basically just form blebs.”

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