Researchers from the Laboratoire d’Analyse et d’Architecture des Systèmes (LAAS-CNRS) and the Institut de Pharmacologie et de Biologie Structurale (IPBS – CNRS/Université de Toulouse III) have measured forces generated by human macrophages migrating in confining microchannels containing deformable micropillar sensors. The results published in Nano Letters reveal an original migration process.
Macrophages are immune cells that migrate in all body tissues. They reach infectious and inflammatory sites to clear out microorganisms and repair injured tissues. Cell migration takes place in complex environments composed of cells and extracellular matrix components scattered with obstacles. Cells squeeze through the matrix and generate pulling or pushing forces on obstacles to move forward. The mechanics of cell migration in 3D environments is poorly understood and their study in vivo is not yet possible.
The researchers from LAAS and from IPBS have collaborated since several years on macrophage migration, which represents a potential therapeutic target in diseases characterized by tissue infiltration of macrophages that contributes to disease progression.
To decipher how human macrophages apply forces in real time to the environment when they infiltrate narrow areas, the researchers designed devices that combine microchannels of controlled dimensions with integrated deformable micropillars. These devices were made in the clean room facility of LAAS-CNRS belonging to the Renatech network.
Macrophage migration in microchannels was monitored by video microscopy and image analysis was developed to measure the deflection and orientation of micropillars, leading to a precision of 60 pico-Newton. By modelling the mechanics of micropillar deflection, the force generated by macrophages was estimated as about 300 pico-Newton.
In microchannels of 6 microns width, the cell nucleus is deformed and cell forces are redirected from inward to outward. It indicates that cells push rather than pull on the environment in narrow channels.
Thanks to this approach, the molecular mechanisms involved in force generation in migrating cells will be investigated, with the objective of identifying targets to control tissue infiltration of macrophages.
Left image : a 6 micron width-channel with micropillars observed by electron microscopy. Middle : a human macrophage inside the channels in contact with micropillars. Top right : a macrophage interacting with three pillars is observed by fluorescence microscopy (nuclei in blue; cell cytoplasm in green). Bottom right : schematic presentation of the orientation of mechanical forces generated by the cell on three representative pillars and showing that the nucleus is deformed by a pillar. ©Renaud Poincloux
Nanoscale forces during confined cell migration. (2018) Desvignes E, Bouissou A, Laborde A, Mangeat T, Proag A, Vieu C, Thibault C, Maridonneau-Parini I and Poincloux R. Nano Letters doi: 10.1021/acs.nanolett.8b02611
Christophe Vieu (LAAS-CNRS) | email@example.com
Isabelle Maridonneau-Parini (IPBS) | Isabelle.Maridonneau-Parini@ipbs.fr
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