Description
Blood cell - vessel wall interactions are critical both for the flow of red blood cells, and for the control of white blood cell adhesion to the walls (e.g. at a site of inflammation). However, the biochemical and mechanical cues governing their tight regulation are still poorly understood, in particular because of the challenge of non-invasive investigation of cell-wall short-range interactions under flow in a complex environment. Using a home-built platform combining advanced biochemical surface functionalization, microfluidics and high-speed interferometric imaging [1], we have investigated experimentally the role of the softness of the vessel wall outer layer in the regulation of blood cell homing under flow. This brush, named glycocalyx and mainly composed of charged exopolysaccharides, is both thick (up to 1µm) and extremely soft (down to a few Pa in compression modulus). We have demonstrated that these peculiar mechanical properties induce a short-range repulsion of non-interacting cells, in good agreement with the theory of elastohydrodynamics that accounts for the effect of substrate deformation under hydrodynamic forces. We have thereby provided the first experimental evidence of this "soft biolubrication" effect at play at small scale [2]. On the other hand, we have shown that these same mechanical properties are a critical factor that stabilizes the homing of cells bearing specific receptors (CD44) for one of the main compound of the glycocalyx, hyaluronan (HA). Furthermore, we have shown that the mechanical barrier created by the glycocalyx screens interactions with surface receptors involved in the adhesion cascade in a CD44-dependent manner. Our results thus highlight the role of the glycocalyx as a gatekeeper for the adhesion to the blood vessel wall.
REFERENCES
[1] H.S. Davies, N.S.Baranova, N.El Amri, L.Coche-Guérente, C.Verdier, L.Bureau, R.P. Richter, D. Débarre, An integrated assay to probe endothelial glycocalyx-blood cell interactions under flow in mechanically and biochemically well-defined environments, Matrix Biol. 78 (2019), 47-59.
[2] H.S. Davies, D. Débarre, N. El Amri, C. Verdier, R.P. Richter, L. Bureau, Elastohydrodynamic lift at a soft wall, Phys Rev Lett 120 (2018), 198001.
[3] H.S. Davies, O. Kirichuk, L. Coche-Guerente, C. Verdier, L. Bureau, D. Débarre, R.P. Richter, Gate keeping at the blood vessel wall, in preparation