Amoeboid Swimming Is Propelled by Molecular Paddling in Lymphocytes

Area of Science:

• Cell Biology
• Biophysics
• Immunology

Background:

• Mammalian cells exhibit mesenchymal (slow, adhesion-dependent) and amoeboid (fast, low-adhesion) migration modes.
• Cell motility is traditionally thought to require substrate interaction (adhesion or friction), precluding swimming.
• Leukocytes and cancer cells utilize the fast amoeboid migration mode.

Purpose of the Study:

• To investigate the mechanism of leukocyte motility, particularly their ability to move in non-adherent environments.
• To challenge the paradigm that cell motility requires substrate adhesion or friction.
• To provide experimental and computational evidence for a swimming mechanism in leukocytes.

Main Methods:

• Experimental observation of leukocyte migration.
• Development of a computational model simulating cell membrane dynamics and protein interactions.
• Analysis of transmembrane protein advection by the actin cortex and vesicular transport.

Main Results:

• Leukocytes swim using a mechanism distinct from cell deformation-driven crawling.
• Propulsion is achieved by rearward and inhomogeneous treadmilling of the cell's external membrane.
• This swimming is powered by transmembrane proteins linked to the actin cortex, with freely diffusing proteins hindering motion.

Conclusions:

• Leukocyte swimming is facilitated by heterogeneous membrane treadmilling, involving molecular paddling and internal recycling of proteins.
• This mechanism explains leukocyte motility in both adherent and non-adherent, confined environments.
• A single machinery of heterogeneous membrane treadmilling can explain the ubiquitous amoeboid migration of mammalian cells.