Human white blood cells use molecular paddles to swim

Date:
September 15, 2020
Source:
Cell Press
Summary:
Human white blood cells, known as leukocytes, swim using a
newly described mechanism called molecular paddling, researchers
report. This microswimming mechanism could explain how both immune
cells and cancer cells migrate in various fluid-filled niches in
the body, for good or for harm.



FULL STORY ========================================================================== Human white blood cells, known as leukocytes, swim using a newly described mechanism called molecular paddling, researchers report in the September
15th issue of Biophysical Journal. This microswimming mechanism could
explain how both immune cells and cancer cells migrate in various
fluid-filled niches in the body, for good or for harm.


==========================================================================
"The capacity of living cells to move autonomously is fascinating and
crucial for many biological functions, but mechanisms of cell migration
remain partially understood," says co-senior study author Olivier Theodoly
of Aix- Marseille University in France. "Our findings shed new light on
the migration mechanisms of amoeboid cells, which is a crucial topic in immunology and cancer research." Cells have evolved different strategies
to migrate and explore their environment. For example, sperm cells,
microalgae, and bacteria can swim through shape deformations or by using
a whip-like appendage called a flagellum. By contrast, somatic mammalian
cells are known to migrate by attaching to surfaces and crawling. It is
widely accepted that leukocytes cannot migrate on 2D surfaces without
adhering to them.

A prior study reported that certain human white blood cells called
neutrophils could swim, but no mechanism was demonstrated. Another study
showed that mouse leukocytes could be artificially provoked to swim. It
is widely thought that cell swimming without a flagellum requires changes
in cell shape, but the precise mechanisms underlying leukocyte migration
have been debated.

In contrast to previous studies, Theodoly, co-senior study author
Chaouqi Misbah of Grenoble Alpes University, and their collaborators
provide experimental and computational evidence in the new study that
human leukocytes can migrate on 2D surfaces without sticking to them
and can swim using a mechanism that does not rely on changes in cell
shape. "Looking at cell motion gives the illusion that cells deform
their body like a swimmer," Misbah says.

"Although leukocytes display highly dynamic shapes and seem to swim
with a breast-stroke mode, our quantitative analysis suggests that these movements are inefficient to propel cells." Instead, the cells paddle
using transmembrane proteins, which span the cell membrane and protrude
outside the cell. The researchers show that membrane treadmilling --
rearward movement of the cell surface -- propels leukocyte migration in
solid or liquid environments, with and without adhesion.

However, the cell membrane does not move like a homogenous treadmill. Some transmembrane proteins are linked to actin microfilaments, which form
part of the cytoskeleton and contract to allow cells to move. The actin cytoskeleton is widely accepted as the molecular engine propelling cell crawling. The new findings demonstrate that actin-bound transmembrane
proteins paddle and propel the cell forward, whereas freely diffusing transmembrane proteins hinder swimming.

The researchers propose that continuous paddling is enabled by
a combination of actin-driven external treadmilling and inner
recycling of actin-bound transmembrane proteins through vesicular
transport. Specifically, the paddling proteins at the rear of the cell
are enclosed inside a vesicle that pinches off from the cell membrane
and transported to the front of the cell. By contrast, the non-paddling transmembrane proteins are sorted out and do not undergo this process
of internal recycling through vesicular transport.

"This recycling of the cell membrane is studied intensively by the
community working on intracellular vesicular traffic, but its role
in motility was hardly considered," Theodoly says. "These functions
of protein sorting and trafficking seemed highly sophisticated for
swimming. Our investigations, to our own surprise, bridge such distant
domains as the physics of microswimmers and the biology of vesicular
traffic." The authors say that molecular paddling could allow immune
cells to thoroughly explore all locations in the body as they migrate
in liquid-filled niches such as swollen body parts, infected bladders, cerebrospinal fluid, or amniotic fluid. Moving forward, the researchers
plan to investigate the functions of molecular paddling in various
environments and assess whether other types of cells use this mode
of migration.


========================================================================== Story Source: Materials provided by Cell_Press. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Laurene Aoun, Alexander Farutin, Nicolas Garcia-Seyda, Paulin
Ne`gre,
Mohd Suhail Rizvi, Sham Tlili, Solene Song, Xuan Luo, Martine
Biarnes- Pelicot, Re'mi Galland, Jean-Baptiste Sibarita, Alphe'e
Michelot, Claire Hivroz, Salima Rafai, Marie-Pierre Valignat,
Chaouqi Misbah, Olivier Theodoly. Amoeboid Swimming Is Propelled
by Molecular Paddling in Lymphocytes. Biophysical Journal, 2020;
119 (6): 1157 DOI: 10.1016/ j.bpj.2020.07.033 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200915133154.htm

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