Human Leukocytes

Human white blood cells, or leukocytes, swim using a newly-described mechanism called molecular paddling, according to new research led by University Grenoble Alpes and Aix Marseille University.

Five types of human leukocytes. Image credit: Syed H. Shirazi et al, doi: 10.3233/THC-161133.

Five types of human leukocytes. Image credit: Syed H. Shirazi et al, doi: 10.3233/THC-161133.

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.

Scientists previously found that certain human white blood cells called neutrophils could swim, but no mechanism was demonstrated. They also 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.

“The capacity of living cells to move autonomously is fascinating and crucial for many biological functions, but mechanisms of cell migration remain partially understood,” said co-lead author Dr. Olivier Theodoly, a researcher at Aix Marseille University.

“Our findings shed new light on the migration mechanisms of amoeboid cells, which is a crucial topic in immunology and cancer research.”

In contrast to previous studies, Dr. Theodoly and colleagues found 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,” said co-lead author Dr. Chaouqi Misbah, a scientist at Grenoble Alpes University.

“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.

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 authors 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,” Dr. Theodoly said.

“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.”

A paper on the findings was published in the Biophysical Journal.

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Laurene Aoun et al. 2020. Amoeboid Swimming Is Propelled by Molecular Paddling in Lymphocytes. Biophysical Journal 119 (6): P1157-1177; doi: 10.1016/j.bpj.2020.07.033

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