Mechanical Strength and Structural Basis of beta(2) Integrin to Mediate Neutrophil Accumulation on Liver Sinusoidal Endothelial Cells: A Study Using Atomic Force Microscopy and Molecular Dynamics Simulations

doi:10.31614/cmes.2018.04079

	Mechanical Strength and Structural Basis of beta(2) Integrin to Mediate Neutrophil Accumulation on Liver Sinusoidal Endothelial Cells: A Study Using Atomic Force Microscopy and Molecular Dynamics Simulations
	Li N(李宁); Zhang X(张潇); Li PW ; Yang H ; Tong CF; Lv SQ(吕守芹); Zhang Y(章燕); Ye ZY ; Pan J ; Long M(龙勉)
刊名	CMES-COMPUTER MODELING IN ENGINEERING & SCIENCES
	2018-08-01
卷号	116 期号:2 页码:263-279
关键词	Liver sinusoidal endothelial cells neutrophils beta(2) integrin shear flow mechanical strength
ISSN号	1526-1492
DOI	10.31614/cmes.2018.04079
英文摘要	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 beta(2) 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-I-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. ICAM-D3-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.
分类号	Q4
URL标识	查看原文
WOS关键词	HEPATIC MICROCIRCULATION ; ICAM-1 BONDS ; I-DOMAIN ; ADHESION ; LFA-1 ; MAC-1 ; INFLAMMATION ; SPECTROSCOPY ; MIGRATION ; BINDING
WOS研究方向	Engineering, Multidisciplinary ; Mathematics, Interdisciplinary Applications
语种	英语
WOS记录号	WOS:000444791300011
资助机构	National Key Research and Development Program of China [2016YFA0501601] ; National Natural Science Foundation of China [31661143044, 31300776] ; Strategic Priority Research Program of Chinese Academy of Sciences [XDB22040101, QYZDJ-SSW-JSC018] ; Visiting Scholar Foundation of the Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education [CQKLBST-2015-002] ; Frontier Science Key Project of Chinese Academy of Sciences [XDB22040101, QYZDJ-SSW-JSC018]
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/77844]
专题	力学研究所_国家微重力实验室
作者单位	1.Chinese Acad Sci, Inst Mech, Natl Micrograv Lab, Ctr Biomech & Bioengn, 15 Beisihuanxi Rd, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, 15 Beisihuanxi Rd, Beijing 100190, Peoples R China 3.Univ Chinese Acad Sci, Sch Engn Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China 4.Chongqing Univ, Key Lab Biorheol Sci & Technol, Minist Educ, 174 Shazhengjie, Chongqing 400044, Peoples R China
推荐引用方式 GB/T 7714	Li N,Zhang X,Li PW,et al. Mechanical Strength and Structural Basis of beta(2) Integrin to Mediate Neutrophil Accumulation on Liver Sinusoidal Endothelial Cells: A Study Using Atomic Force Microscopy and Molecular Dynamics Simulations[J]. CMES-COMPUTER MODELING IN ENGINEERING & SCIENCES,2018,116(2):263-279.
APA	李宁.,张潇.,Li PW.,Yang H.,Tong CF.,...&龙勉.(2018).Mechanical Strength and Structural Basis of beta(2) Integrin to Mediate Neutrophil Accumulation on Liver Sinusoidal Endothelial Cells: A Study Using Atomic Force Microscopy and Molecular Dynamics Simulations.CMES-COMPUTER MODELING IN ENGINEERING & SCIENCES,116(2),263-279.
MLA	李宁,et al."Mechanical Strength and Structural Basis of beta(2) Integrin to Mediate Neutrophil Accumulation on Liver Sinusoidal Endothelial Cells: A Study Using Atomic Force Microscopy and Molecular Dynamics Simulations".CMES-COMPUTER MODELING IN ENGINEERING & SCIENCES 116.2(2018):263-279.