Two Complementary Signaling Pathways Depict Eukaryotic Chemotaxis: A Mechanochemical Coupling Model

doi:10.3389/fcell.2021.786254

	Two Complementary Signaling Pathways Depict Eukaryotic Chemotaxis: A Mechanochemical Coupling Model
	Zhou LW(周吕文)4,5,6; Feng SL(冯世亮)4,5,6; Li L(李龙)2,3; Lv SQ(吕守芹)1,4,5; Zhang Y(章燕)1,4,5; Long M(龙勉)1,4,5
刊名	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
	2021-11-17
卷号	9 页码:12
关键词	chemotaxis cytoskeletal remodeling mathematical model biochemical biomechanical
ISSN号	2296-634X
DOI	10.3389/fcell.2021.786254
通讯作者	Li, Long(lilong@lnm.imech.ac.cn) ; Long, Mian(mlong@imech.ac.cn)
英文摘要	Many eukaryotic cells, including neutrophils and Dictyostelium cells, are able to undergo correlated random migration in the absence of directional cues while reacting to shallow gradients of chemoattractants with exquisite precision. Although progress has been made with regard to molecular identities, it remains elusive how molecular mechanics are integrated with cell mechanics to initiate and manipulate cell motility. Here, we propose a two dimensional (2D) cell migration model wherein a multilayered dynamic seesaw mechanism is accompanied by a mechanical strain-based inhibition mechanism. In biology, these two mechanisms can be mapped onto the biochemical feedback between phosphoinositides (PIs) and Rho GTPase and the mechanical interplay between filamin A (FLNa) and FilGAP. Cell migration and the accompanying morphological changes are demonstrated in numerical simulations using a particle-spring model, and the diffusion in the cell membrane are simulations using a one dimensional (1D) finite differences method (FDM). The fine balance established between endogenous signaling and a mechanically governed inactivation scheme ensures the endogenous cycle of self-organizing pseudopods, accounting for the correlated random migration. Furthermore, this model cell manifests directional and adaptable responses to shallow graded signaling, depending on the overwhelming effect of the graded stimuli guidance on strain-based inhibition. Finally, the model cell becomes trapped within an obstacle-ridden spatial region, manifesting a shuttle run for local explorations and can chemotactically "escape", illustrating again the balance required in the complementary signaling pathways.
分类号	一类
资助项目	National Natural Science Foundation of China[12002176] ; National Natural Science Foundation of China[32130061] ; National Natural Science Foundation of China[11972200] ; National Natural Science Foundation of China[11902327] ; Opening fund of State Key Laboratory of Nonlinear Mechanics (LNM) of Chinese Academy of Sciences, Frontier Science Key Project of Chinese Science Academy[QYZDJ-SSW-JSC018] ; Youth Innovation Promotion Association CAS
WOS关键词	CELL-MIGRATION ; FOCAL ADHESIONS ; POLARIZATION ; NEUTROPHILS ; MECHANOSENSITIVITY ; MECHANISMS ; DYNAMICS ; RIGIDITY ; INSIGHTS ; POLARITY
WOS研究方向	Cell Biology ; Developmental Biology
语种	英语
WOS记录号	WOS:000726135700001
资助机构	National Natural Science Foundation of China ; Opening fund of State Key Laboratory of Nonlinear Mechanics (LNM) of Chinese Academy of Sciences, Frontier Science Key Project of Chinese Science Academy ; Youth Innovation Promotion Association CAS
其他责任者	Li, Long ; Long, Mian
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/88061]
专题	力学研究所_国家微重力实验室力学研究所_非线性力学国家重点实验室
作者单位	1.Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engineered Construct & Mechanobio, Beijing, Peoples R China; 3.Chinese Acad Sci, Inst Mech, State Key Lab Nonlinear Mech LNM, Beijing, Peoples R China; 4.Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing Key Lab Engn Construct & Mechaobiol, Beijing, Peoples R China; 5.Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Key Lab Micrograv, Beijing, Peoples R China; 6.Ningbo Univ, Sch Mech Engn & Mech, Smart Mat & Adv Struct Lab, Ningbo, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Zhou LW,Feng SL,Li L,et al. Two Complementary Signaling Pathways Depict Eukaryotic Chemotaxis: A Mechanochemical Coupling Model[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2021,9:12.
APA	周吕文,冯世亮,李龙,吕守芹,章燕,&龙勉.(2021).Two Complementary Signaling Pathways Depict Eukaryotic Chemotaxis: A Mechanochemical Coupling Model.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9,12.
MLA	周吕文,et al."Two Complementary Signaling Pathways Depict Eukaryotic Chemotaxis: A Mechanochemical Coupling Model".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021):12.