Theoretical modeling of trail formation of a migrating neutrophil on substrate

doi:10.1007/s10409-023-22461-x

	Theoretical modeling of trail formation of a migrating neutrophil on substrate
	Zhang XN(张晓宁); Hu WR(胡文瑞); Gao WB(高文博); Zhang Y(章燕); Long M(龙勉)
刊名	ACTA MECHANICA SINICA ; 6
	2023-06
卷号	39 页码:622461
关键词	Neutrophil migration Trail formation Theoretical modeling Numerical calculation Parametric analysis
ISSN号	0567-7718
DOI	10.1007/s10409-023-22461-x
英文摘要	Neutrophils undergo fast migration dynamics onto endothelium or extracellular matrix using anterior protrusion together with posterior contraction and retraction. While these migrating cells tend to leave behind the long-lasting membranous trails with enriched integrins ripped down from cell body, it is still unclear how the trail formation is quantitatively correlated with cell migration and what the regulating factors are key in this process. Here a multi-layered mechanochemical model was integrated with a motor-clutch model to simulate numerically the chemotactic migration of a neutrophil on the substrate. Results indicated that, in response to those polarized distributions of sensing molecule P21-activated kinase 1 (PAK1) and the downstream molecules Ras-related C3 botulinum toxin substrate (Rac) and Ras homolog family member (RhoA), membrane-bound integrins tend to be accumulated at both the cell front and rear, promoting the increase of migrating velocity and trail number with time when actin-related protein2/3 complex (Arp2/3) and myosin are respectively accumulated at the front and rear. These predictions were in agreement with those typical experimental observations in integrin polarization and trail formation. Parametric analysis further proposed that, while the migrating velocity yields a biphasic dependence on substrate hardness and motor unloaded velocity, trail number increases monotonically with substrate hardness, on-rate of integrin-ligand bonds, motor unloaded velocity, motor stall force, and clutch number but decreases with chemokine concentration and off-rate of integrin-ligand bonds. This work provided an insight in elaborating the mechanochemical pathways in neutrophil migration and deciphering the key extracellular or intracellular factors in regulating the relevant trail formation of those migrating neutrophils.
分类号	二类
WOS研究方向	Engineering, Mechanical ; Mechanics
语种	英语
WOS记录号	WOS:001003556600001
资助机构	National Natural Science Foundation of China [31627804, 11772345, 91539119] ; Scientific Instrument Developing Project of the Chinese Academy of Sciences [GJJSTU20220002] ; Frontier Science Key Project of Chinese Science Academy [QYZDJ-SSW-JSC018]
其他责任者	Zhang, Y ; Long, M (corresponding author), Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing Key Lab Engn Construct & Mechanobiol, Beijing 100190, Peoples R China. ; Zhang, Y ; Long, M (corresponding author), Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China. ; Zhang, Y ; Long, M (corresponding author), Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China.
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/92411]
专题	力学研究所_国家微重力实验室
作者单位	1.{Zhang Xiaoning, Zhang Yan, Long Mian} Univ Chinese Acad Sci Sch Engn Sci Beijing 100049 Peoples R China 2.{Zhang Xiaoning, Hu Wenhui, Gao Wenbo, Zhang Yan, Long Mian} Chinese Acad Sci Inst Mech Key Lab Micrograv Natl Micrograv Lab Beijing 100190 Peoples R China 3.{Zhang Xiaoning, Hu Wenhui, Gao Wenbo, Zhang Yan, Long Mian} Chinese Acad Sci Inst Mech Ctr Biomech & Bioengn Beijing Key Lab Engn Construct & Mechanobiol Beijing 100190 Peoples R China
推荐引用方式 GB/T 7714	Zhang XN,Hu WR,Gao WB,et al. Theoretical modeling of trail formation of a migrating neutrophil on substrate[J]. ACTA MECHANICA SINICA, 6,2023,39:622461.
APA	张晓宁,胡文瑞,高文博,章燕,&龙勉.(2023).Theoretical modeling of trail formation of a migrating neutrophil on substrate.ACTA MECHANICA SINICA,39,622461.
MLA	张晓宁,et al."Theoretical modeling of trail formation of a migrating neutrophil on substrate".ACTA MECHANICA SINICA 39(2023):622461.