TY - EJOU AU - Li, Ning AU - Zhang, Xiao AU - Li, Peiwen AU - Yang, Hao AU - Tong, Chunfang AU - Lü, Shouqin AU - Zhang, Yan AU - Ye, Zhiyi AU - Pan, Jun AU - Long, Mian TI - Mechanical Strength and Structural Basis of β2 Integrin to Mediate Neutrophil Accumulation on Liver Sinusoidal Endothelial Cells: A Study Using Atomic Force Microscopy and Molecular Dynamics Simulations T2 - Computer Modeling in Engineering \& Sciences PY - 2018 VL - 116 IS - 2 SN - 1526-1506 AB - Neutrophil (PMN) accumulation on liver sinusoidal endothelial cells (LSECs) is crucial to pathogen clearance and tissue damage in the liver sinusoids and controlled by a series of adhesion molecules expressed on the surface of PMNs and LSECs. The role of lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) in this process is still contentious. Here we compared the dynamic force spectra of the binding of β2 integrin to intercellular adhesion molecule-1 (ICAM-1) on LSECs using atomic force microscopy (AFM) and performed free and steered molecular dynamics (MD) simulations to analyze their structural bases of LFA-1- or Mac-1-I-domain and ICAM-1-D1 or D3 pair in their force spectra. Our AFM data suggest that the mechanical strength of LFA-1-ICAM-1 bond is significantly stronger than that of Mac-1-ICAM-1 bond, implying a dominate role for LFA-1 to mediate PMN adhesion under shear flow. MD simulations indicated that spontaneous dissociation of Mac-1-I-domain vs. ICAMD3-domain is slower with the stronger interaction energy than that for LFA-1 I-domain vs. ICAM-D1-domain and that the rupture force for Mac-1 is lower than that for LFA-1, which are in qualitative agreement with the above experimental observations. These data indicate that the biomechanical features of LFA-1 and Mac-1 to mediate PMN adhesion on LSECs in vitro are similar with those in other tissues like cerebrovascular endothelium, while Mac-1-mediated PMN recruitment in liver sinusoids may stem from the slow blood flow in vivo. These findings further the understandings of PMN recruitment under shear flow in liver sinusoids. KW - Liver sinusoidal endothelial cells KW - neutrophils KW - β2 integrin KW - shear flow KW - mechanical strength DO - 10.31614/cmes.2018.04079