High-resolution laboratory experiments show how cells ‘eat’

A new study shows how cell membranes curve to create “mouths” that allow cells to consume things that surround them.

“Just as our eating habits basically shape everything in our body, the way cells ‘eat’ means for the health of the cells,” said Comert Kural, associate professor of physics at Ohio State University and lead author of the study. “And scientists have so far not understood the mechanics behind how it happened.”

The study, recently published in the journal Developmental Cell, found that a cell’s intercellular machinery assembles into a highly curved basket-like structure that eventually grows into a closed cage. Scientists had previously thought that the structure began as a flat lattice.

Membrane curvature is important, Kural said: It controls the formation of the pockets that carry substances in and out of a cell.

The pockets capture substances around the cell and form around the extracellular substances before they become vesicles – small sacs one millionth the size of a red blood cell. Vesicles transport important things for a cell’s health – for example proteins – into the cell. But they can also be hijacked by pathogens that can infect cells.

But the question of how these pockets were formed by membranes previously thought to be flat had hindered researchers for nearly 40 years.

“It was a controversy in cellular studies,” Kural said. “And we were able to use super-resolution fluorescence imaging to actually see these pockets form in living cells, and then we could answer the question of how they are created.

“Simply put, unlike previous studies, we made high-resolution films of cells instead of taking snapshots,” Kural said. “Our experiments revealed that protein scaffolds begin to deform the underlying membrane as soon as they are recruited to the sites of vesicle formation.”

This is in contrast to previous hypotheses that the protein scaffolds in a cell had to undergo an energy-intensive reorganization in order for the membrane to bend, Kural said.

The way cells consume and expel vesicles plays a key role for living organisms. The process helps remove bad cholesterol from the blood; it also transmits neural signals. The process is known to break down into several diseases, including cancer and Alzheimer’s disease.

“It is important to understand the origin and dynamics of membrane-bound vesicles – they can be used to deliver drugs for medical purposes, but at the same time hijacked by pathogens such as viruses to penetrate and infect cells,” Kural said. “Our results matter, not only for our understanding of the basic principles of life, but also for developing better therapeutic strategies.”

Emanuele Cocucci, an assistant professor at Ohio State College of Pharmacy, co-authored this study with researchers from UC Berkeley, UC Riverside, Iowa State University, Purdue University, and the Chinese Academy of Sciences.

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