Starting: September 2015
A prevailing dogma in biology is that cells of the immune system (i.e. leukocytes) use the adhesion machinery in order to crawl on a substrate towards infections. While such crawling behaviour seems to be an essential process for leukocytes motion along the endothelium, it has been recently revealed in laboratory experiments that the expression of adhesion molecules like integrins is not required for the motion of these cells, thus calling into question the crawling paradigm.
Migrating leukocytes in fluids, as well as in gels, were observed to undergo frequent shape changes (described as amoeboid) that enable them to “swim” without the assistance of adhesion sites, a motion that will be referred to as amoeswimming (in order to distinguish it from other well-known swimming modes using flagella and cilia activity).
The exact nature of amoeswimming, which consists in a combination of swimming in tissue interstices and leaning on cell membranes and on extracellular matrix, is a largely unexplored topic. The project consists in designing controlled experiments with a progressive refinement of concepts in order to study the amoeswimming of leukocytes in media with increasing degrees of complexity:
1. a “simple” fluid, in order to analyze the pure amoeswimming strategy and efficiency, as a function of confinement,
2. confined geometries with soft boundaries mimicking interstices of tissues bounded by deformable cellular membranes,
3. an unconfined geometry in the presence of a gel (collagen), by varying collagen concentration until attaining a regime which resembles real tissues.
A systematic confrontation with simulations, based on the boundary integral method as well as on the immersed boundary technique, will be undertaken.
The project consists in a rational approach, by isolating the different decisive effects entering the locomotion process, without ignoring their interactions. Experiments and modelling will work in a concerted fashion relying on the expertise of the Laboratory for Interdisciplinary Physics which combines mechanical, physical and biological concepts.
This project, carried out at the laboratory LIPhy, aims at making pioneering breakthroughs by unravelling the intricate strategy of cellular motion in complex media.