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Vinculin mediated mechanosensing at focal adhesions

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Vinculin mediated mechanosensing at focal adhesions

Surface Topography Modulates Cell mechanosensing of Extracellular Matrix

中国化学会-生物物理化学专业委员会第四届全国生物物理化...

作者：严洁 National University of Singapore

Force sensing is crucial for cells to regulate their adhesions to extracellular matrix（ECM） through integrin based focal adhesions（FA）. Vinculin is a crucial protein mediating mechanosensing at FA through binding to talin, a force-bearing cytoplasmic adapters that links FA to actin network. The vinculin’s mechanosensing function relies complex interactions with its many binding partners, which however are suppressed due to a strong interaction between the vinculin head domains（D1-D4） and the tail（Vt） domain. It has been hypothesized that binding of the vinculin D1（VD1） domain to mechanically stretched talin is needed for releasing the auto-inhibited conformation of vinculin. Here we tested this hypothesis by direct single-molecule measurements of force-dependent binding of full-length vinculin to mechanically stretched talin, and confirmed it by showing that this binding can stabilize vinculin in a D1-Vt dissociated state at ＞ 5 pN forces that expose the cinculin binding sites（VBS） in talin.

关键词： mechanosensing Focal adhesion Vinclulin Talin alpha-catenin

来源： cnki会议评论

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医用生物力学 2019年第A1期34卷 36-36页

作者： Bianxiao Cui Xiao Li Wei Zhang Lasse Hyldgaard Klausen Francesca Santoro Zhao Wenting Department of Chemistry Stanford University

The interaction between the cell membrane and the extracellular matrix is crucial for many cellular functions by modulating mechanosensitive signaling *** properties of the extracellular matrix such as stiffness and topography affect such *** recent work reveals that surface topography of tens to hundreds of nanometer scale modulates cell signaling by activating intracellular curvature-sensitive *** use vertical nanostructures protruding from a flat surface as a platform to induce precise curvatures on the cell membrane and to probe biological processes in live *** nanopillars deform the plasma membrane inwards and induce membrane curvature when the cell engulfs them,leading to a reduction of the membrane-substrate gap *** found that the high membrane curvature induced by vertical nanopillars significantly affects the distribution of curvature-sensitive proteins and stimulates several cellular processes in live cells including cellular endocytosis and cytoskeleton *** studies show a strong interplay between biological cells and nano-featured surfaces,which is an essential consideration for future development of interfacing devices.

关键词： Surface Topography Modulates Cell mechanosensing of Extracellular Matrix

A novel electrospinning method for self-assembled tree-like fibrous scaffolds:Microenvironment-associated regulation of MSC behavior and bone regeneration

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Journal of Materials Science & Technology 2022年第20期115卷 52-70页

作者： Jeong In Kim Ju Yeon Kim Sung-Ho Kook Jeong-Chae Lee Cluster for Craniofacial Development and Regeneration Research Institute of Oral Biosciences and School of DentistryJeonbuk National UniversityJeonju 54896Republic of Korea Department of Bionanosystem Engineering Jeonbuk National UniversityJeonju 54896Republic of Korea Department of Bioactive Material Sciences Research Center of Bioactive MaterialsJeonbuk National UniversityJeonju 54896Republic of Korea

Numerous studies highlight advantages of electrospun scaffolds in bone tissue engineering,in which cellular behavior is tightly affected by fiber topographical cues of ***,the classic electrospinning setup limits a desired presentation of biomimetic fibrous microenvironments that sense mechanosignaling and regulate stem cell *** aims of this study were to fabricate advanced asspun scaffolds presenting tree-like microfiber/nanonet networks and to evaluate their regulatory potentials on behavior of human mesenchymal stem cells(h MSCs)and bone *** we developed a novel electrospinning setup that allowed the presentation of patterned Trunk microfibers(TMF)and/or branched nanonet fibers(BNn Fs)in biomimetic fibrous *** the cellular mechanisms,anisotropichierarchical topography of TMF controlled behavior of h MSCs through focal adhesion formation and Yesassociated protein(YAP)induction,whereas BNn F disturbed such mechanosensing responses in the *** fiber microenvironment-related expression and nuclear localization of YAP *** correlated with the potentials of as-spun scaffolds to enhance osteogenic differentiation of the h MSCs and alveolar bone defect healing in an animal ***,this study provides an advanced approach of the modified electrospinning setup for presentation of biomimetic fibrillar microenvironments in as-spun scaffolds along with their application in stem cell behavior regulation and regenerative tissue engineering.

关键词： Electrospinning Advanced biomimetic scaffolds Stem cell behavior mechanosensing Bone tissue engineering

Biomechanical control of lymphatic vessel physiology and functions

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Cellular & Molecular Immunology 2023年第9期20卷 1051-1062页

作者： Veronique Angeli Hwee Ying Lim Immunology Translational Research Programme Yong Loo Lin School of MedicineDepartment of Microbiology and ImmunologyNational University of SingaporeSingaporeSingapore Immunology Programme Life Sciences InstituteNational University of SingaporeSingaporeSingapore

The ever-growing research on lymphatic biology has clearly identified lymphatic vessels as key players that maintain human health through their functional roles in tissue fluid homeostasis,immunosurveillance,lipid metabolism and *** is therefore not surprising that the list of human diseases associated with lymphatic malfunctions has grown larger,including issues beyond lymphedema,a pathology traditionally associated with lymphatic drainage ***,the discovery of factors and pathways that can promote optimal lymphatic functions may offer new therapeutic *** evidence indicates that aside from biochemical factors,biomechanical signals also regulate lymphatic vessel expansion and functions ***,we review how mechanical forces induced by fluid shear stress affect the behavior and functions of lymphatic vessels and the mechanisms lymphatic vessels employ to sense and transduce these mechanical cues into biological signals.

关键词： lymphatic vessel biomechanical force mechanosensing mechanotransduction human diseases

Functions and clinical significance of mechanical tumor microenvironment:cancer cell sensing,mechanobiology and metastasis

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Cancer Communications 2022年第5期42卷 374-400页

作者： Hanying Zhou Meng Wang Yixi Zhang Qingqing Su Zhengxin Xie Xiangyan Chen Ran Yan Ping Li Tingting Li Xiang Qin Hong Yang ChunhuiWu Fengming You Shun Li Yiyao Liu Department of Biophysics School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengduSichuan 610054P.R.China Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese MedicineChengduSichuan 610072P.R.China

Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid *** this process,the tumormicroenvironment(TME)fractures cellular and matrix architecture normality through biochemical and mechanical means,abetting tumorigenesis and treatment *** cells sense and respond to the strength,direction,and duration of mechanical cues in the TME by various mechanotransduction ***,far less understood is the comprehensive perspective of the functions and mechanisms of *** to the great therapeutic difficulties brought by the mechanical changes in the TME,emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves,which has been proven to be a potential therapeutic *** this review,we discussed the origins and roles ofmechanical factors in the TME,cell sensing,mechano-biological coupling and signal transduction,in vitro construction of the tumormechanicalmicroenvironment,applications and clinical significance in the TME.

关键词： tumor microenvironment mechanical model mechanosensing mechanotransduction cytoskeleton remodelin

Mechanical force drives the polarization and orientation of cells

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Acta Mechanica Sinica 2019年第2期35卷 275-288页

作者： Shijie He Xiaomeng Li Baohua Ji Center for Engineering in Medicine Massachusetts General Hospital Harvard Medical School Boston MA 02114 USA Department of Applied Mechanics School of Aerospace Engineering Beijing Institute of Technology Beijing 100081 China Department of Engineering Mechanics Zhejiang University Hangzhou 310027 China

Collective cells are organized to form specific patterns which play important roles in various physiological and pathological processes, such as tissue morphogenesis, wound healing, and cancer invasion. Compared to single cell behaviors, which has been intensively studied from many aspects (cell migration, adhesion, polarization, proliferation, etc.) and at various scales (molecular, subcellular, and cellular), the multiple cell behaviors are relatively less understood, particularly in a quantitative manner. In this paper, we will present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling, including those cell behaviors on/in 2D and 3D substrate/tissue. We find that the collective cell behaviors, including polarization, alignment and migration are closely related to local stress states in cell layer or tissue, which demonstrate the crucial roles of mechanical forces in the living organisms. Specifically, the cells prefer to polarize and align along the maximum principal stress in the cell layer, and the aspect ratio of cell increases with the in-plane maximum shear stress, suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation. This theory of stress-driven cell behaviors of polarization and orientation provides a new perspective for understanding cell behaviors in living organisms and the guideline for tissue engineering in biomedical applications.

关键词： Collective cell behaviors Cell polarization Cell alignment Quantification Cell mechanosensing

Joining actions: crosstalk between intermediate filaments and actin orchestrates cellular physical dynamics and signaling

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Science China(Life Sciences) 2019年第10期62卷 1368-1374页

作者： Jian Li Yun Zou Zhifang Li Yaming Jiu CAS Key Laboratory of Molecular Virology and Immunology Institut Pasteur of ShanghaiChinese Academy of Sciences Shanghai 200031China University of Chinese Academy of Sciences Beijing 100049China

Many key cellular functions are regulated by the interplay of three distinct cytoskeletal networks, made of actin filaments,microtubules, and intermediate filaments(IFs), which is a hitherto poorly investigated area of research. However, there are growing evidence in the last few years showing that the IFs cooperate with actin filaments to exhibit strongly coupled *** review recapitulates our current knowledge on how the crosstalk between IFs and actin filaments modulates the migration properties, mechano-responsiveness and signaling transduction of cells, from both biophysical and biochemical point of view.

关键词： intermediate filaments actin cytoskeletal interaction cell migration signaling pathway cell mechanosensing

Mineral Fabrication and Golgi Apparatus Activity in <i>Spirostomum ambiguum</i>: A Primordial Paradigm of the Stressed Bone Cell?

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Journal of Biomedical Science and Engineering 2017年第10期10卷 466-483页

作者： Valerie Fallon Philippa E. Garner Jean E. Aaron Institute of Membrane and Systems Biology Faculty of Biological Sciences University of Leeds Leeds UK

The histological basis for acute osteocyte mechanosensitivity remains uncertain. A novel bone cell model of mechanotransduction and inorganic trafficking may be the powerful, silt-burrowing protozoan Spirostomum ambiguum which when being physically challenged fabricates within vesicles populations of bone-like calcium phosphate microspheres, about 1 μm in diameter. These not only attribute considerable compression-resilience but also resemble the Golgi-directed mineral assemblies we recently reported in osteocytes. Advantageously, calcification in the protozoan (confirmed by ultramicroscopy with EDX elemental microanalysis) enabled Golgi comparison under overt, natural phases of both high (i.e. silt-tunnelling) and low (i.e free-swimming) stress. Established hard-tissue microscopy techniques previously positive in bone cells included quantitative fluorescent tetracycline labelling for bone salt together with the same metazoan Golgi body marker (Green Fluorescent Protein-tagged mannosidase II construct). Organellar modulation was monitored by transfection of live organisms in situ (some post-stained with red nuclear fluorochrome TOPRO-3). Results showed that GFP-tagged Golgi fluorescence increased from swimmers (mean 74.5 ± SD 6.7 AU) to burrowers (mean 104.6 ± SD 2.7;p < 0.0001) synchronous with juxtanuclear tetracycline-labelled mineral fluorescence (swimmers, mean 89.7 ± SD 3.3 AU;burrowers, mean 138.0 ± SD 4.0;p < 0.0001). Intracellular dense microspheres, single or bridged, were harvested as pellets rich in Ca, P (Ca:P 0.98) and Si, their polarised alignment moving from transaxial in swimmers to axial in burrowers. It was concluded that Golgi-directed mineral fabrication in the large, accessible, silt-enclosed ciliate resembles that in the smaller, less-accessible bone cell and may be a conserved early mechanobiological intracellular development predicating force translation into compression-resistant mineral fabrication in loaded segments of the osteocyte synci

关键词： Golgi-Directed Calcification mechanosensing Protozoan Osteocyte Model Tetracycline Fluorochrome for Bone Mineral GFP Fluorochrome for Golgi Apparatus

Discovery of Aquaporin-3 as a sperm protein essential for postcopulatory sperm osmoadaptation

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Discovery of Aquaporin-3 as a sperm protein essential for po...