Gravity-Vector Induces Mechanical Remodeling of rMSCs via Combined Substrate Stiffness and Orientation

doi:10.3389/fbioe.2021.724101

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	Gravity-Vector Induces Mechanical Remodeling of rMSCs via Combined Substrate Stiffness and Orientation
	Zhang C(张晨)1,2; Lv DY(吕东媛)1,2,3 ; Zhang F(张帆)1,2,3 ; Wu Y(武亿)1,2,3; Zheng L(郑鲁)1,2,3; Zhang XY(张晓宇)1,2,3; Li Z(李展)1,2 ; Sun SJ(孙树津)1,2,3 ; 龙勉Mian 1,2,3
通讯作者	Long, Mian(mlong@imech.ac.cn)
发表期刊	FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
	2022-02-07
卷号	9 页码:14
ISSN	2296-4185
摘要	Distinct physical factors originating from the cellular microenvironment are crucial to the biological homeostasis of stem cells. While substrate stiffness and orientation are known to regulate the mechanical remodeling and fate decision of mesenchymal stem cells (MSCs) separately, it remains unclear how the two factors are combined to manipulate their mechanical stability under gravity vector. Here we quantified these combined effects by placing rat MSCs onto stiffness-varied poly-dimethylsiloxane (PDMS) substrates in upward (180 degrees), downward (0 degrees), or edge-on (90 degrees) orientation. Compared with those values onto glass coverslip, the nuclear longitudinal translocation, due to the density difference between the nucleus and the cytosol, was found to be lower at 0 degrees for 24 h and higher at 90 degrees for 24 and 72 h onto 2.5 MPa PDMS substrate. At 0 degrees, the cell was mechanically supported by remarkably reduced actin and dramatically enhanced vimentin expression. At 90 degrees, both enhanced actin and vimentin expression worked cooperatively to maintain cell stability. Specifically, perinuclear actin stress fibers with a large number, low anisotropy, and visible perinuclear vimentin cords were formed onto 2.5 MPa PDMS at 90 degrees for 72 h, supporting the orientation difference in nuclear translocation and global cytoskeleton expression. This orientation dependence tended to disappear onto softer PDMS, presenting distinctive features in nuclear translocation and cytoskeletal structures. Moreover, cellular morphology and focal adhesion were mainly affected by substrate stiffness, yielding a time course of increased spreading area at 24 h but decreased area at 72 h with a decrease of stiffness. Mechanistically, the cell tended to be stabilized onto these PDMS substrates via beta 1 integrin-focal adhesion complexes-actin mechanosensitive axis. These results provided an insight in understanding the combination of substrate stiffness and orientation in defining the mechanical stability of rMSCs.
关键词	substrate stiffness orientation mechanosensing nucleus translocation cytoskeletal remodeling focal adhesion complex reorganization cellular morphology
DOI	10.3389/fbioe.2021.724101
收录类别	SCI ; EI
语种	英语
WOS记录号	WOS:000760640500001
关键词[WOS]	STEM-CELLS ; DIFFERENTIAL REGULATION ; ELASTICITY ; MORPHOLOGY ; ADHESION ; FATE
WOS研究方向	Biotechnology & Applied Microbiology ; Science & Technology - Other Topics
WOS类目	Biotechnology & Applied Microbiology ; Multidisciplinary Sciences
论文分区	二类/Q1
力学所作者排名	1
RpAuthor	Long, Mian
引用统计	被引频次：1[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/311007/88749
专题	微重力重点实验室
作者单位	1.Chinese Acad Sci, Key Lab Micrograv, Ctr Biomech & Bioengn, Natl Micrograv Lab, Beijing, Peoples R China; 2.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, 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	Zhang C,Lv DY,Zhang F,et al. Gravity-Vector Induces Mechanical Remodeling of rMSCs via Combined Substrate Stiffness and Orientation[J]. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY,2022,9:14.
APA	张晨.,吕东媛.,张帆.,武亿.,郑鲁.,...&龙勉Mian.(2022).Gravity-Vector Induces Mechanical Remodeling of rMSCs via Combined Substrate Stiffness and Orientation.FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY,9,14.
MLA	张晨,et al."Gravity-Vector Induces Mechanical Remodeling of rMSCs via Combined Substrate Stiffness and Orientation".FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 9(2022):14.

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