Mechanochemical modeling of neutrophil migration based on four signaling layers, integrin dynamics, and substrate stiffness

doi:10.1007/s10237-018-1047-2

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	Mechanochemical modeling of neutrophil migration based on four signaling layers, integrin dynamics, and substrate stiffness
	Feng SL(冯世亮)1,2,3; Zhou LW(周吕文)1,2,3; Zhang Y(章燕)1,2,3 ; Lv SQ(吕守芹)1,2,3 ; Long M(龙勉)1,2,3
通讯作者	Long, Mian(mlong@imech.ac.cn)
发表期刊	BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
	2018-12-01
卷号	17 期号:6 页码:1611-1630
ISSN	1617-7959
摘要	Directional neutrophil migration during human immune responses is a highly coordinated process regulated by both biochemical and biomechanical environments. In this paper, we developed an integrative mathematical model of neutrophil migration using a lattice Boltzmann-particle method built in-house to solve the moving boundary problem with spatiotemporal regulation of biochemical components. The mechanical features of the cell cortex are modeled by a series of spring-connected nodes representing discrete cell-substrate adhesive sites. The intracellular signaling cascades responsible for cytoskeletal remodeling [e.g., small GTPases, phosphoinositide-3-kinase (PI3K), and phosphatase and tensin homolog] are built based on our previous four-layered signaling model centered on the bidirectional molecular transport mechanism and implemented as reaction-diffusion equations. Focal adhesion dynamics are determined by force-dependent integrin-ligand binding kinetics and integrin recycling and are thus integrated with cell motion. Using numerical simulations, the model reproduces the major features of cell migration in response to uniform and gradient biochemical stimuli based on the quantitative spatiotemporal regulation of signaling molecules, which agree with experimental observations. The existence of multiple types of integrins with different binding kinetics could act as an adaptation mechanism for substrate stiffness. Moreover, cells can perform reversal, U-turn, or lock-on behaviors depending on the steepness of the reversal biochemical signals received. Finally, this model is also applied to predict the responses of mutants in which PTEN is overexpressed or disrupted.
关键词	Chemotaxis Cytoskeletal remodeling Mathematical model Biochemical Biomechanical
DOI	10.1007/s10237-018-1047-2
收录类别	SCI ; EI
语种	英语
WOS记录号	WOS:000452359300005
关键词[WOS]	EUKARYOTIC CHEMOTAXIS ; CELL-MIGRATION ; MATHEMATICAL-MODEL ; LFA-1 ACTIVATION ; FOCAL ADHESIONS ; ACTIN DYNAMICS ; RAC ACTIVATION ; RHO-GTPASES ; MOTILITY ; POLARIZATION
WOS研究方向	Biophysics ; Engineering
WOS类目	Biophysics ; Engineering, Biomedical
资助项目	National Natural Science Foundation of China[31230027] ; National Natural Science Foundation of China[91539119] ; National Natural Science Foundation of China[11502272] ; National Key Research and Development Program of China[2016YFA0501601] ; Frontier Science Key Project[QYZDJ-SSW-JSC018] ; Strategic Priority Research Program Grant[XDB22040101]
项目资助者	National Natural Science Foundation of China ; National Key Research and Development Program of China ; Frontier Science Key Project ; Strategic Priority Research Program Grant
论文分区	二类
力学所作者排名	1
RpAuthor	Long, Mian
引用统计	被引频次：12[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/311007/78952
专题	微重力重点实验室
作者单位	1.Chinese Acad Sci, Ctr Biomech & Bioengn, Key Lab Micrograv, Natl Micrograv Lab, Beijing, Peoples R China; 2.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mech, Beijing, Peoples R China; 3.Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Feng SL,Zhou LW,Zhang Y,et al. Mechanochemical modeling of neutrophil migration based on four signaling layers, integrin dynamics, and substrate stiffness[J]. BIOMECHANICS AND MODELING IN MECHANOBIOLOGY,2018,17,6,:1611-1630.
APA	冯世亮,周吕文,章燕,吕守芹,&龙勉.(2018).Mechanochemical modeling of neutrophil migration based on four signaling layers, integrin dynamics, and substrate stiffness.BIOMECHANICS AND MODELING IN MECHANOBIOLOGY,17(6),1611-1630.
MLA	冯世亮,et al."Mechanochemical modeling of neutrophil migration based on four signaling layers, integrin dynamics, and substrate stiffness".BIOMECHANICS AND MODELING IN MECHANOBIOLOGY 17.6(2018):1611-1630.

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