@Article{cmes.2018.04079, AUTHOR = {Ning Li, Xiao Zhang, Peiwen Li, Hao Yang, Chunfang Tong, Shouqin Lü, Yan Zhang, Zhiyi Ye, Jun Pan, *, Mian Long, *}, TITLE = {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}, JOURNAL = {Computer Modeling in Engineering \& Sciences}, VOLUME = {116}, YEAR = {2018}, NUMBER = {2}, PAGES = {263--279}, URL = {http://www.techscience.com/CMES/v116n2/33850}, ISSN = {1526-1506}, ABSTRACT = {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. }, DOI = {10.31614/cmes.2018.04079} }