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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
Corresponding AuthorLong, Mian(mlong@imech.ac.cn)
Source PublicationBIOMECHANICS AND MODELING IN MECHANOBIOLOGY
2018-12-01
Volume17Issue:6Pages:1611-1630
ISSN1617-7959
AbstractDirectional 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.
KeywordChemotaxis Cytoskeletal remodeling Mathematical model Biochemical Biomechanical
DOI10.1007/s10237-018-1047-2
Indexed BySCI ; EI
Language英语
WOS IDWOS:000452359300005
WOS KeywordEUKARYOTIC CHEMOTAXIS ; CELL-MIGRATION ; MATHEMATICAL-MODEL ; LFA-1 ACTIVATION ; FOCAL ADHESIONS ; ACTIN DYNAMICS ; RAC ACTIVATION ; RHO-GTPASES ; MOTILITY ; POLARIZATION
WOS Research AreaBiophysics ; Engineering
WOS SubjectBiophysics ; Engineering, Biomedical
Funding ProjectNational 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]
Funding OrganizationNational Natural Science Foundation of China ; National Key Research and Development Program of China ; Frontier Science Key Project ; Strategic Priority Research Program Grant
Classification二类
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Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/78953
Collection国家微重力实验室
Affiliation1.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
Recommended Citation
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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