A new study shows how cell membranes curve to create the "mouths" that allow
the cells to consume things that surround them.
"Just like our eating habits basically shape anything in our body, the way
cells 'eat' matters for the health of the cells," said Comert Kural,
associate professor of physics at The Ohio State University and lead author
of the study. "And scientists did not, until now, understand the mechanics
of how that happened."
The study, published last month in the journal Developmental Cell, found
that the intercellular machinery of a cell assembles into a highly curved
basket-like structure that eventually grows into a closed cage. Scientists
had previously believed that structure began as a flat lattice.
Membrane curvature is important, Kural said: It controls the formation of
the pockets that carry substances into and out of a cell.
The pockets capture substances around the cell, forming around the
extracellular substances, before turning into vesicles—small sacs one-one
millionth the size of a red blood cell. Vesicles carry important things for
a cell's health—proteins, for example—into the cell. But they can also be
hijacked by pathogens that can infect cells.
But the question of how those pockets formed from membranes that were
previously believed to be flat had stymied 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 watch these pockets
form within live cells, and so we could answer that question of how they are
created.
"Simply put, in contrast to the previous studies, we made high-resolution
movies of cells instead of taking snapshots," Kural said. "Our experiments
revealed that protein scaffolds start deforming the underlying membrane as
soon as they are recruited to the sites of vesicle formation."
That contrasts with previous hypotheses that the protein scaffolds of a cell
had to go through an energy-intensive reorganization in order for the
membrane to curve, Kural said.
The way cells consume and expel vesicles plays a key role for living
organisms. The process helps clear bad cholesterol from blood; it also
transmits neural signals. The process is known to break down in several
diseases, including cancer and Alzheimer's disease.
"Understanding the origin and dynamics of membrane-bound vesicles is
important—they can be utilized for delivering drugs for medicinal purposes,
but at the same time, hijacked by pathogens such as viruses to enter and
infect cells," Kural said. "Our results matter, not only for our
understanding of the fundamentals of life, but also for developing better
therapeutic strategies."
Emanuele Cocucci, an assistant professor in Ohio State's College of
Pharmacy, co-authored this study, along with researchers from UC Berkeley,
UC Riverside, Iowa State University, Purdue University and the Chinese
Academy of Sciences.
Reference:
Nathan M. Willy et al, De novo endocytic clathrin coats develop curvature at
early stages of their formation, Developmental Cell (2021).
DOI: 10.1016/j.devcel.2021.10.019