期刊
BIOPHYSICAL JOURNAL
卷 119, 期 6, 页码 1157-1177出版社
CELL PRESS
DOI: 10.1016/j.bpj.2020.07.033
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资金
- French Agence Nationale de la Recherche [RECRUTE ANR-15-CE15-0022, ILIAAD ANR-18-CE09-0029]
- LABEX INFORM
- Region Sud, the Turing Centre for Living systems
- Excellence Initiative of Aix-Marseille University A*MIDEX
- French Investissements d'Avenir'' programme
- company Alveole
- French Agence Nationale de la Recherche (Investments for the future) [ANR-10-INBS-04-01]
- French National Research Agency [ANR-10-INBS-04]
- Centre National d'Etudes Spatiales
- European Space Agency
- French-German university programme Living Fluids [CFDA-Q1-14]
Mammalian cells developed two main migration modes. The slow mesenchymatous mode, like crawling of fibroblasts, relies on maturation of adhesion complexes and actin fiber traction, whereas the fast amoeboid mode, observed exclusively for leukocytes and cancer cells, is characterized by weak adhesion, highly dynamic cell shapes, and ubiquitous motility on two-dimensional and in three-dimensional solid matrix. In both cases, interactions with the substrate by adhesion or friction are widely accepted as a prerequisite for mammalian cell motility, which precludes swimming. We show here experimental and computational evidence that leukocytes do swim, and that efficient propulsion is not fueled by waves of cell deformation but by a rearward and inhomogeneous treadmilling of the cell external membrane. Our model consists of a molecular paddling by transmembrane proteins linked to and advected by the actin cortex, whereas freely diffusing transmembrane proteins hinder swimming. Furthermore, continuous paddling is enabled by a combination of external treadmilling and selective recycling by internal vesicular transport of cortex-bound transmembrane proteins. This mechanism explains observations that swimming is five times slower than the retrograde flow of cortex and also that lymphocytes are motile in nonadherent confined environments. Resultantly, the ubiquitous ability of mammalian amoeboid cells to migrate in two dimensions or three dimensions and with or without adhesion can be explained for lymphocytes by a single machinery of heterogeneous membrane treadmilling.
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