Mechanical probing of individual adhesion molecules

F. Rico

Leukocytes travel at high velocities with the blood flow and slow down within milliseconds by interacting with the vessel wall via adhesion molecules [1,2]. This fast process of bond formation and rupture is crucial during the early steps of the immune response. Different adhesion complexes are involved during the leukocyte adhesion cascade, such as integrins and selectins [3]. While the unbinding response at µm/s velocities and below is well known, little is known at the physiological velocities in the mm/s regime. Moreover, little or none attention has been given to the unfolding of its ligands during the unbinding process. We combine various approaches, such as high-speed force spectroscopy [4,5], acoustic force spectroscopy [6] and molecular dynamics simulations [7–9] to probe the mechanics of adhesion complexes at the single molecule level.

[1]        A. S. Popel and P. C. Johnson, Annual Review of Fluid Mechanics 37, 43 (2005).
[2]        R. Alon and M. L. Dustin, Immunity 26, 17 (2007).
[3]        K. Ley, C. Laudanna, M. I. Cybulsky, and S. Nourshargh, Nat Rev Immunol 7, 678 (2007).
[4]        F. Rico, L. Gonzalez, I. Casuso, M. Puig-Vidal, and S. Scheuring, Science 342, 741 (2013).
[5]        F. Sumbul, A. Marchesi, H. Takahashi, S. Scheuring, and F. Rico, in Nanoscale Imaging: Methods and Protocols, edited by Y. L. Lyubchenko (Springer New York, New York, NY, 2018), pp. 243–264.
[6]        G. Sitters, D. Kamsma, G. Thalhammer, M. Ritsch-Marte, E. J. G. Peterman, and G. J. L. Wuite, Nat Meth 12, 47 (2015).
[7]        H. Takahashi, F. Rico, C. Chipot, and S. Scheuring, ACS Nano 12, 2719 (2018).
[8]        F. Sumbul and F. Rico, Methods in Molecular Biology (2018).
[9]        F. Rico, A. Russek, L. Gonzalez, H. Grubmuller, and S. Scheuring, ArXiv:1808.07122 [Physics, q-Bio] (2018).


This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 772257).