Generation and Regulation of Microtubule Network Asymmetry to Drive Cell Polarity Joyce C
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Kinesin-4 KIF21B Limits Microtubule Growth to Allow Rapid Centrosome
RESEARCH ARTICLE Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells Peter Jan Hooikaas1†, Hugo GJ Damstra1†, Oane J Gros1, Wilhelmina E van Riel1‡, Maud Martin1§, Yesper TH Smits2, Jorg van Loosdregt2, Lukas C Kapitein1, Florian Berger1*, Anna Akhmanova1* 1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands; 2Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands Abstract When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of *For correspondence: microtubule dynamics contributes to this process. Here, we show that the knockout of KIF21B, a [email protected] (FB); kinesin-4 linked to autoimmune disorders, causes microtubule overgrowth and perturbs [email protected] (AA) centrosome translocation. KIF21B restricts microtubule length by inducing microtubule pausing typically followed by catastrophe. Catastrophe induction with vinblastine prevented microtubule †These authors contributed overgrowth and was sufficient to rescue centrosome polarization in KIF21B-knockout cells. equally to this work Biophysical simulations showed that a relatively small number of KIF21B molecules can restrict ‡ Present address: Netherlands mirotubule length and promote an imbalance -
1. Introduction to Cell Biology Me239 Statistics
1. introduction to cell biology me239 statistics some information about yourself • 41.7% undergrad • average year: 3.7 • 58.3% grad student • average year: 1.3 • 58.3% ME • 41.7% BME + 1 BioE i am taking this class because • I am interested in cells • I am interested in mechanics • I want to learn how to describe cells mechanically • I want to learn how the mechanical environment influences the cell cell mechanics is primarily part of my... • 29.2% research • 87.5% coursework the inner life of a cell, viel & lue, harvard [2006] me239 mechanics of the cell 1 me239 mechanics of the cell 2 me239 statistics me239 statistics background in cell biology and mechanics what particular cells are you interested in and why... • cells mostly undergrad coursework (75.0%), high school classes. some have • cardiomyocytes ... clinical implications, prevalence of cardiac disease taken graduate level classes (12.5%) and done research related to cell biology • stem cells ... potential benefit for patients suffering from numerous conditions • mechanics almost all have a solid mechanics background from either under- • read blood cells ... i think they are cool graduate degrees (75.0%) or graduate classes (25.0%). • neural cells ... i love the brain • skin cells, bone cells, cartilage cells three equations that you consider most important in mechanics • hooks law / more generally constitutive equations which scales are you most interested in? • 12.5% cellular scale and smaller • newton’s second law – more generally equilibrium equations • 45.8% cellular scale -
Quantitative Methodologies to Dissect Immune Cell Mechanobiology
cells Review Quantitative Methodologies to Dissect Immune Cell Mechanobiology Veronika Pfannenstill 1 , Aurélien Barbotin 1 , Huw Colin-York 1,* and Marco Fritzsche 1,2,* 1 Kennedy Institute for Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7LF, UK; [email protected] (V.P.); [email protected] (A.B.) 2 Rosalind Franklin Institute, Harwell Campus, Didcot OX11 0FA, UK * Correspondence: [email protected] (H.C.-Y.); [email protected] (M.F.) Abstract: Mechanobiology seeks to understand how cells integrate their biomechanics into their function and behavior. Unravelling the mechanisms underlying these mechanobiological processes is particularly important for immune cells in the context of the dynamic and complex tissue microen- vironment. However, it remains largely unknown how cellular mechanical force generation and mechanical properties are regulated and integrated by immune cells, primarily due to a profound lack of technologies with sufficient sensitivity to quantify immune cell mechanics. In this review, we discuss the biological significance of mechanics for immune cells across length and time scales, and highlight several experimental methodologies for quantifying the mechanics of immune cells. Finally, we discuss the importance of quantifying the appropriate mechanical readout to accelerate insights into the mechanobiology of the immune response. Keywords: mechanobiology; biomechanics; force; immune response; quantitative technology Citation: Pfannenstill, V.; Barbotin, A.; Colin-York, H.; Fritzsche, M. Quantitative Methodologies to Dissect 1. Introduction Immune Cell Mechanobiology. Cells The development of novel quantitative technologies and their application to out- 2021, 10, 851. https://doi.org/ standing scientific problems has often paved the way towards ground-breaking biological 10.3390/cells10040851 findings. -
Cell Architecture: Putting the Building Blocks Together
COCEBI-1090; NO. OF PAGES 3 Available online at www.sciencedirect.com Cell architecture: putting the building blocks together Editorial overview Anna Akhmanova and Tim Stearns Current Opinion in Cell Biology 2012, 25:xx–yy 0955-0674/$ – see front matter, # 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ceb.2012.12.003 Anna Akhmanova Cell Biology, Faculty of Science, Utrecht In considering cell architecture it is important to realize that for cells, as for University, Padualaan 8, 3584 CH Utrecht, buildings, the underpinning for the external shape is provided by a complex The Netherlands internal superstructure. And for cells, this cytoskeletal underpinning must e-mail: [email protected] be highly dynamic to effect the changes in morphology and organization associated with division, growth and differentiation. Cytoskeletal elements Anna Akhmanova is Professor of Cell Biology at Utrecht University, the Netherlands, and a were some of the first components of intracellular structure described by member of EMBO. Her lab uses cell early microscopists in the late 19th century, but it was not until a century biological approaches, in vitro reconstitutions later that the remarkable complexity of the cytoskeleton, in both compo- and high-resolution microscopy to study sition and behavior, has been revealed. Advances in genomics and proteo- molecular mechanisms of microtubule mics have provided us with near-comprehensive lists of the molecular dynamics and vesicle trafficking and their players associated with the various cytoskeletal systems. The challenge contribution to mammalian development and human disease. now is to understand how these components work together, and this is one of the central themes of this issue of Current Opinion in Cell Biology. -
Cell Mechanics: from Cytoskeletal Dynamics to Tissue-Scale Mechanical Phenomena
Syracuse University SURFACE Physics - Dissertations College of Arts and Sciences 5-2013 Cell Mechanics: From Cytoskeletal Dynamics to Tissue-Scale Mechanical Phenomena Shiladitya Banerjee Follow this and additional works at: https://surface.syr.edu/phy_etd Recommended Citation Banerjee, Shiladitya, "Cell Mechanics: From Cytoskeletal Dynamics to Tissue-Scale Mechanical Phenomena" (2013). Physics - Dissertations. 131. https://surface.syr.edu/phy_etd/131 This Dissertation is brought to you for free and open access by the College of Arts and Sciences at SURFACE. It has been accepted for inclusion in Physics - Dissertations by an authorized administrator of SURFACE. For more information, please contact [email protected]. Syracuse University SUrface Physics - Dissertations College of Arts and Sciences 5-1-2013 Cell Mechanics: From Cytoskeletal Dynamics to Tissue-Scale Mechanical Phenomena Shiladitya Banerjee [email protected] Follow this and additional works at: http://surface.syr.edu/phy_etd Recommended Citation Banerjee, Shiladitya, "Cell Mechanics: From Cytoskeletal Dynamics to Tissue-Scale Mechanical Phenomena" (2013). Physics - Dissertations. Paper 131. This Dissertation is brought to you for free and open access by the College of Arts and Sciences at SUrface. It has been accepted for inclusion in Physics - Dissertations by an authorized administrator of SUrface. For more information, please contact [email protected]. Abstract This dissertation explores the mechanics of living cells, integrating the role of intracellular activity to capture the emergent mechanical behav- ior of cells. The topics covered in this dissertation fall into three broad categories : (a) intracellular mechanics, (b) interaction of cells with the extracellular matrix and (c) collective mechanics of multicellular colonies. In part (a) I propose theoretical models for motor-filament interactions in the cell cytoskeleton, which is the site for mechanical force generation in cells. -
EMBO Facts & Figures
excellence in life sciences Reykjavik Helsinki Oslo Stockholm Tallinn EMBO facts & figures & EMBO facts Copenhagen Dublin Amsterdam Berlin Warsaw London Brussels Prague Luxembourg Paris Vienna Bratislava Budapest Bern Ljubljana Zagreb Rome Madrid Ankara Lisbon Athens Jerusalem EMBO facts & figures HIGHLIGHTS CONTACT EMBO & EMBC EMBO Long-Term Fellowships Five Advanced Fellows are selected (page ). Long-Term and Short-Term Fellowships are awarded. The Fellows’ EMBO Young Investigators Meeting is held in Heidelberg in June . EMBO Installation Grants New EMBO Members & EMBO elects new members (page ), selects Young EMBO Women in Science Young Investigators Investigators (page ) and eight Installation Grantees Gerlind Wallon EMBO Scientific Publications (page ). Programme Manager Bernd Pulverer S Maria Leptin Deputy Director Head A EMBO Science Policy Issues report on quotas in academia to assure gender balance. R EMBO Director + + A Conducts workshops on emerging biotechnologies and on H T cognitive genomics. Gives invited talks at US National Academy E IC of Sciences, International Summit on Human Genome Editing, I H 5 D MAN 201 O N Washington, DC.; World Congress on Research Integrity, Rio de A M Janeiro; International Scienti c Advisory Board for the Centre for Eilish Craddock IT 2 015 Mammalian Synthetic Biology, Edinburgh. Personal Assistant to EMBO Fellowships EMBO Scientific Publications EMBO Gold Medal Sarah Teichmann and Ido Amit receive the EMBO Gold the EMBO Director David del Álamo Thomas Lemberger Medal (page ). + Programme Manager Deputy Head EMBO Global Activities India and Singapore sign agreements to become EMBC Associate + + Member States. EMBO Courses & Workshops More than , participants from countries attend 6th scienti c events (page ); participants attend EMBO Laboratory Management Courses (page ); rst online course EMBO Courses & Workshops recorded in collaboration with iBiology. -
1 Introduction to Cell Biology
1 Introduction to cell biology 1.1 Motivation Why is the understanding of cell mechancis important? cells need to move and interact with their environment ◦ cells have components that are highly dependent on mechanics, e.g., structural proteins ◦ cells need to reproduce / divide ◦ to improve the control/function of cells ◦ to improve cell growth/cell production ◦ medical appli- cations ◦ mechanical signals regulate cell metabolism ◦ treatment of certain diseases needs understanding of cell mechanics ◦ cells live in a mechanical environment ◦ it determines the mechanics of organisms that consist of cells ◦ directly applicable to single cell analysis research ◦ to understand how mechanical loading affects cells, e.g. stem cell differentation, cell morphology ◦ to understand how mechanically gated ion channels work ◦ an understanding of the loading in cells could aid in developing struc- tures to grow cells or organization of cells more efficiently ◦ can help us to understand macrostructured behavior better ◦ can help us to build machines/sensors similar to cells ◦ can help us understand the biology of the cell ◦ cell growth is affected by stress and mechanical properties of the substrate the cells are in ◦ understanding mechan- ics is important for knowing how cells move and for figuring out how to change cell motion ◦ when building/engineering tissues, the tissue must have the necessary me- chanical properties ◦ understand how cells is affected by and affects its environment ◦ understand how mechanical factors alter cell behavior (gene expression) -
A Review of Single-Cell Adhesion Force Kinetics and Applications
cells Review A Review of Single-Cell Adhesion Force Kinetics and Applications Ashwini Shinde 1 , Kavitha Illath 1, Pallavi Gupta 1, Pallavi Shinde 1, Ki-Taek Lim 2 , Moeto Nagai 3 and Tuhin Subhra Santra 1,* 1 Department of Engineering Design, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India; [email protected] (A.S.); [email protected] (K.I.); [email protected] (P.G.); [email protected] (P.S.) 2 Department of Biosystems Engineering, Kangwon National University, Chuncheon-Si, Gangwon-Do 24341, Korea; [email protected] 3 Department of Mechanical Engineering, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580, Japan; [email protected] * Correspondence: [email protected]; Tel.: +91-044-2257-4747 Abstract: Cells exert, sense, and respond to the different physical forces through diverse mechanisms and translating them into biochemical signals. The adhesion of cells is crucial in various develop- mental functions, such as to maintain tissue morphogenesis and homeostasis and activate critical signaling pathways regulating survival, migration, gene expression, and differentiation. More impor- tantly, any mutations of adhesion receptors can lead to developmental disorders and diseases. Thus, it is essential to understand the regulation of cell adhesion during development and its contribution to various conditions with the help of quantitative methods. The techniques involved in offering different functionalities such as surface imaging to detect forces present at the cell-matrix and deliver quantitative parameters will help characterize the changes for various diseases. Here, we have briefly reviewed single-cell mechanical properties for mechanotransduction studies using standard and recently developed techniques. -
Meeting Booklet
LS2 Annual Meeting 2019 “Cell Biology from Tissue to Nucleus” Meeting Booklet 14-15 February, University of Zurich, Campus Irchel LS 2 - Life Sciences Switzerland Design by Dagmar Bocakova - [email protected] 2019 WELCOME ADDRESS Dear colleagues and friends It is with great pleasure that we invite you to the LS² Annual Meeting 2019, held on the 14th and 15th of February, 2019 at the Irchel Campus of the University of Zurich. This is a special year, as it is the 50th anniversary of USGEB/LS2, which we will celebrate with a Jubilee Apéro on Thursday 14th. The LS² Annual Meeting brings together scientists from all nations and backgrounds to discuss a variety of Life Science subjects. The meeting this year focusses on the cell in health and disease, with plenary talks on different aspects of cell biology and a symposium on live cell imaging approaches. You will be able to hear the latest, most exciting findings in several fields, from Molecular and Cellular Biosciences, Proteomics, Chemical Biology, Physiology, Pharmacology and more, presented by around 30 invited speakers and 45 speakers selected from abstracts in one of the seven scientific symposia and five plenary lectures. Two novelties highlight the meeting this year: The "PIs of Tomorrow" session, in which selected postdocs will present their research to a jury of professors, will be for the first time a plenary session. In addition, poster presenters will be selected to give flash talks in the symposia with the spirit to further promote young scientists. Join us for the poster session with more than 130 posters, combined with a large industry exhibition and the Jubilee Apéro. -
Emerging Views of the Nucleus As a Cellular Mechanosensor Tyler J
Emerging views of the nucleus as a cellular mechanosensor Tyler J. Kirby1,2 and Jan Lammerding1,2 1 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 2 Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York Correspondence to: Jan Lammerding, PhD Cornell University Weill Institute for Cell and Molecular Biology Nancy E. and Peter C. Meinig School of Biomedical Engineering Weill Hall, Room 235 Ithaca, NY 14853 USA Abstract The ability of cells to respond to mechanical forces is critical for numerous biological processes. Emerging evidence indicates that external mechanical forces trigger changes in nuclear envelope structure and composition, chromatin organization, and gene expression. However, it remains unclear if these processes originate in the nucleus or are downstream of cytoplasmic signals. This review discusses recent findings supporting a direct role of the nucleus in cellular mechanosensing and highlights novel tools to study nuclear mechanotransduction. 1 Introduction Cells are constantly being exposed to mechanical forces, such as shear forces on endothelial cells1, compressive forces on chondrocytes2, and tensile forces in myocytes3. The cells’ ability to sense and respond to these mechanical cues are critical for numerous biological processes, including embryogenesis4, 5, development4, 5, and tissue homeostasis6, 7. While it has long been recognized that mechanical forces can influence cell morphology and behavior8, 9, the understanding of the -
Mitotic Cells Contract Actomyosin Cortex and Generate Pressure to Round Against Or Escape Epithelial Confinement
ARTICLE Received 28 Feb 2015 | Accepted 12 Oct 2015 | Published 25 Nov 2015 DOI: 10.1038/ncomms9872 OPEN Mitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement Barbara Sorce1, Carlos Escobedo1,2, Yusuke Toyoda3, Martin P. Stewart1,4,5, Cedric J. Cattin1, Richard Newton1, Indranil Banerjee6, Alexander Stettler1, Botond Roska6, Suzanne Eaton3, Anthony A. Hyman3, Andreas Hierlemann1 & Daniel J. Mu¨ller1 Little is known about how mitotic cells round against epithelial confinement. Here, we engineer micropillar arrays that subject cells to lateral mechanical confinement similar to that experienced in epithelia. If generating sufficient force to deform the pillars, rounding epithelial (MDCK) cells can create space to divide. However, if mitotic cells cannot create sufficient space, their rounding force, which is generated by actomyosin contraction and hydrostatic pressure, pushes the cell out of confinement. After conducting mitosis in an unperturbed manner, both daughter cells return to the confinement of the pillars. Cells that cannot round against nor escape confinement cannot orient their mitotic spindles and more likely undergo apoptosis. The results highlight how spatially constrained epithelial cells prepare for mitosis: either they are strong enough to round up or they must escape. The ability to escape from confinement and reintegrate after mitosis appears to be a basic property of epithelial cells. 1 Department of Biosystems Science and Engineering, Eidgeno¨ssische Technische Hochschule (ETH) Zurich, Mattenstrasse 26, Basel 4058, Switzerland. 2 Department of Chemical Engineering, Queen’s University, 19 Division Street, Kingston, Ontario, Canada K7L 3N6. 3 Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. -
Connecting the Nucleus to the Cytoskeleton by SUN–KASH
COCEBI-1074; NO. OF PAGES 6 Available online at www.sciencedirect.com Connecting the nucleus to the cytoskeleton by SUN–KASH bridges across the nuclear envelope Erin C Tapley and Daniel A Starr The nuclear–cytoskeleton connection influences many aspects with a wide variety of cytoskeletal components [11]. of cellular architecture, including nuclear positioning, the Mutations in mammalian SUN and KASH proteins lead stiffness of the global cytoskeleton, and mechanotransduction. to developmental defects in neurogenesis, gametogen- Central to all of these processes is the assembly and function of esis, myogenesis, cilliogenesis, and retina formation and conserved SUN–KASH bridges, or LINC complexes, that span contribute to human diseases, including muscular dystro- the nuclear envelope. Recent studies provide details of the phy, ataxia, Progeria, lissencephaly, and cancer higher order assembly and targeting of SUN proteins to the [11,17,18,19,20 ]. inner nuclear membrane. Structural studies characterize SUN– KASH interactions that form the central link of the nuclear- The rapidly growing field of nuclear–cytoskeletal inter- envelope bridge. KASH proteins at the outer nuclear membrane actions has recently been reviewed [11–13]. Here, with link the nuclear envelope to the cytoskeleton where forces are apologies to the rest of the field, we focus on five major generated to move nuclei. Significantly, SUN proteins were findings reported over the past two years. The first step of recently shown to contribute to the progression of building the SUN–KASH bridge is recruiting SUN laminopathies. proteins to the inner nuclear membrane. Surprisingly, trafficking SUN proteins to the inner nuclear membrane Address involves multiple, partially redundant mechanisms Department of Molecular and Cellular Biology, University of California, [21 ,22 ,23 ].