Revealing Molecular Forces in Cell Rolling Adhesion

Synopsis

Rolling adhesion is the behaviour that white blood cells (WBC) exhibit as they passively roll along blood vessel walls under flow. It plays a critical role in capturing cells in the blood, guiding them toward inflammation sites. Rolling adhesion is mediated by catch-bond interactions between selectins expressed on blood vessels walls and PSGL-1 on WBC. Despite our understanding of individual components of this process, how biology utilize these molecular mechanical interaction remain experimentally unexplored. Here, we developed 2 methods that map the functional adhesion sites and their strength on a leukocyte surface. The first method relies on tracking the rotational angle of a single rolling cell, which confers advantages over standard methods that track the centre-of-mass alone. Constructing the adhesion map from the instantaneous angular velocity reveals that the adhesion profile along the rolling circumference is inhomogeneous. We corroborated these findings with a second method that allowed us to obtain a footprint of molecular adhesion events using DNA-based molecular force probes. Our results reveal that adhesion at the functional level is not uniformly distributed over the leukocyte surface as previously assumed, but is instead patchy. Lastly, I will discuss our recent work on the interpretation and future improvement of non-equilibrium molecular force sensors.