Authors: Lining Ju, Yunfeng Chen, Lingzhou Xue, Xiaoping Du, Cheng Zhu
Summary:
How cells sense their mechanical environment and transduce forces into biochemical signals is a crucial yet unresolved question in mechanobiology. Platelets use receptor glycoprotein Ib (GPIb), specifically its α subunit (GPIbα), to signal as they tether and translocate on von Willebrand factor (VWF) of injured arterial surfaces against blood flow. Force slows VWF-GPIbα dissociation (catch bond) and unfolds the GPIbα leucine-rich repeat domain (LRRD) and juxtamembrane mechanosensitive domain (MSD). How these mechanical processes trigger biochemical signals remains unknown. Here we analyze these extracellular events and the resulting intracellular Ca2+ on a single platelet in real time, revealing that LRRD unfolding intensifies the Ca2+ signal analogously whereas MSD unfolding determines the Ca2+ type digitally. The >30nm macroglycopeptide separating the two domains transmits VWF-GPIbα bond lifetime prolonged by LRRD unfolding to enhance MSD unfolding cooperatively at an optimal force, which may serve as a design principle for a generic mechanosensory machine.
Source:
eLife; 2016, 5