Leukocytes travel at high velocities with the blood flow and slow down within milliseconds by interacting with the vessel wall via adhesion molecules [1]. This fast formation and rupture of bonds is crucial during the early steps of the immune response. One of the essential leukocyte adhesion complexes is the pair formed by the integrin αLβ2 and intercellular adhesion molecule-1 (ICAM-1) [2]. While the unbinding response is well known [3], little or none attention has been given to possible unfolding of the 5 immunoglobulin-like domains of ICAM-1 during the unbinding process. The main goal of this work is to determine the molecular mechanisms of the unfolding of leukocyte adhesion molecules at high loading rates. For that, we combined high-speed force spectroscopy (HS-FS), allowing mm/s pulling rates and µs time resolution [4,5], and all-atom steered molecular dynamics (SMD) simulations at overlapping rates providing an atomic description of the process supported by experimental results. HS-FS measurements and SMD simulations allowed us to determine the forces required to unfold ICAM-1. Experiments and simulations showed good agreement indicating that domain 3 unfolds first at forces lower than the unbinding forces of αLβ2/ICAM-1 at similar loading rates. This suggests that ICAM-1 partially unfolds before complex rupture, regulating leukocyte adhesion by buffering the applied force, working as a shock nanoabsorber.