Researchers report in the Biophysical Journal that human white blood cells, known as leukocytes, swim using a newly identified process called molecular paddling.
This process of microswimming could explain how both immune cells and cancer cells migrate, for good or ill, into various fluid-filled niches in the body.
“The ability of living cells to move autonomously is fascinating and crucial for many biological functions, but the mechanisms of cell migration are only partially understood,” said co-senior study author Olivier Theodoly of the University of Aix-Marseille in France. “Our results shed new light on the migration mechanisms of amoeboid cells, which is an important topic in immunology and cancer research.”
In order to migrate and discover their environment, cells have developed various strategies.
For example, by changing shape or using a whip-like appendage called a flagellum, sperm cells, microalgae and bacteria can swim.
Mammalian somatic cells, on the other hand, are known to migrate by binding to surfaces and creeping.
It is widely agreed that leukocytes can not move without binding to them on 2D surfaces.
A previous study stated that neutrophils, some human white blood cells, can swim, but no mechanism was seen.
Another research found that mouse leukocytes can be artificially provoked to swim.
The swimming of cells without flagella is widely believed to entail changes in cell shape, but the exact mechanisms underlying leukocyte migration remain controversial.
This is a 3D video-microscopy of a swimming lymphocyte cytoskeleton. It displays protrusions traveling around the body of the cell, imitating the motion of a breast swimming.
Credit: Microscopy by SoSPIM: L.
Hey, Aoun, O.
About Theodoly, M.
R. Galland, Biarnes
In comparison to previous research, in the new study, Theodoly, co-study author Chaouqi Misbah of the University of Grenoble Alps, and their collaborators provide experimental and computer proof that human leukocytes can migrate without sticking to 2D surfaces and that they can swim with a mechanism that does not depend on cell shape changes. “When you look at the movement of cells, you get the illusion that cells deform their bodies like a swimmer,” says Misbah. “Although leukocytes have highly dynamic shapes and appear to swim with a breaststroke mode, our quantitative analysis suggests that these motions are inefficient to propel the cells.”
Instead, transmembrane proteins that cross the cell membrane and protrude outside the cell are used to paddle the cells.
Researchers have shown that leukocyte migration is guided by membrane treading – the backward movement of the cell surface – in solid or liquid conditions, with or without adhesion.
However, like a homogeneous treadmill, the cell membrane does not move. Actin microfilaments, which are part of the cytoskeleton and contract to allow cells to pass, are associated with certain transmembrane proteins.
The molecular motor that drives cell crawling is generally known to be the actin cytoskeleton.
The new findings show that actin-bound transmembrane proteins paddle and move the cell forward, while swimming is hindered by freely diffusing transmembrane proteins.
This video shows the picture of paddling molecules being streamed backwards outside the cell.
Credit: Microscopy by TIRF: N. Garcia-Seyda
The researchers suggest that continuous paddling is made possible by a combination of external actin-driven pedaling and internal recycling by vesicular transport of actin-bound transmembrane proteins. Specifically, in the posterior part of the cell, paddling proteins are stuck in a vesicle that laces off the cell membrane and is transferred to the anterior part of the cell.
The non-paddling transmembrane proteins, on the other hand, are sorted out and do not undergo this internal recycling process through vesicular transport.
“This recycling of the cell membrane has been studied extensively by the community studying intracellular vesicular trafficking, but its role in motility has received little attention,” says Theodoly. “These functions of protein sorting and trafficking appeared to be very challenging for swimming. Our studies, to our own surprise, bridge domains as distant as the physics of microswimming and the biology of vesicular trafficking.”
The authors note that molecular immune cell paddling