Molecular dynamics simulation of shear- and stretch-induced dissociation of P-selectin/PSGL-1 complex

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	Molecular dynamics simulation of shear- and stretch-induced dissociation of P-selectin/PSGL-1 complex
	Kang YY(康英永); Lv SQ(吕守芹); Ren P(任鹏); Huo B(霍波); Long M(龙勉); Huo, B (reprint author), Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100080, Peoples R China.
发表期刊	BIOPHYSICAL JOURNAL
	2012-01-04
卷号	102 期号:1 页码:112-120
ISSN	0006-3495
摘要	By mediating the tethering and rolling of leukocytes on vascular surfaces, the interactions between P-selectin and the P-selectin glycoprotein ligand 1 (PSGL-1) play crucial roles during inflammation cascade. Tensile stretch produced by rolling leukocytes and shear stress exerted by blood flow constitute the two types of mechanical forces that act on the P-selectin/PSGL-1 bond. These forces modulate not only dissociation kinetics of this bond, but also the leukocyte adhesion dynamics. However, the respective contribution of the two forces to bond dissociation and to the corresponding microstructural bases remains unclear. To mimic the mechanical microenvironment, we developed two molecular dynamics approaches;namely, an approach involving the shear flow field with a controlled velocity gradient, and the track dragging approach with a defined trajectory. With each approach or with both combined, we investigate the microstructural evolution and dissociation kinetics of the P-LE/SGP-3 construct, which is the smallest functional unit of the P-selectin/PSGL-1 complex. The results demonstrate that both shear flow and tensile stretch play important roles in the collapse of the construct and that, before bond dissociation, the former causes more destruction of domains within the construct than the latter. Dissociation of the P-LE/SGP-3 construct features intramolecular destruction of the epidermal-growth-factor (EGF) domain and the breaking of hydrogen-bond clusters at the P-selectin-lectin/EGF interface. Thus, to better understand how mechanics impacts the dissociation kinetics of the P-selectin/PSGL-1 complex, we propose herein two approaches to mimic its physiological mechanical environment.
关键词	Selectin Glycoprotein Ligand-1 Granule Membrane-protein P-selectin Cell-adhesion Beta-switch Endothelial-cells Catch Bonds Ib-alpha Flow Transition
学科领域	生物力学
URL	查看原文
收录类别	SCI
语种	英语
WOS记录号	WOS:000298825400014
项目资助者	This work was supported by the National Natural Science Foundation of China (30970707, 10702075, and 30730032), the National High-Technology Research and Development Program of China 2009AA02Z407), the National Key Basic Research Foundation of China (2011CB710904), and the Knowledge Innovation Project of the Chinese Academy of Sciences (KJCX2-YW-L08).
课题组名称	NML分子-细胞生物力学与空间生命科学
论文分区	一类
引用统计	被引频次：10[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://dspace.imech.ac.cn/handle/311007/46556
专题	微重力重点实验室
通讯作者	Huo, B (reprint author), Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100080, Peoples R China.
推荐引用方式 GB/T 7714	Kang YY,Lv SQ,Ren P,et al. Molecular dynamics simulation of shear- and stretch-induced dissociation of P-selectin/PSGL-1 complex[J]. BIOPHYSICAL JOURNAL,2012,102,1,:112-120.
APA	Kang YY,Lv SQ,Ren P,Huo B,Long M,&Huo, B .(2012).Molecular dynamics simulation of shear- and stretch-induced dissociation of P-selectin/PSGL-1 complex.BIOPHYSICAL JOURNAL,102(1),112-120.
MLA	Kang YY,et al."Molecular dynamics simulation of shear- and stretch-induced dissociation of P-selectin/PSGL-1 complex".BIOPHYSICAL JOURNAL 102.1(2012):112-120.

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