Molecular Mechanics of Immune Cells

Michael Sixt's laboratory is interested in morphodynamic processes both at the cellular and at the tissue level. We mainly focus on the immune system and try to understand the molecular and mechanical principles underlying leukocyte dynamics during processes such as migration and intercellular communication. Here we work at the interface of cell biology, immunology and biophysics and currently investigate how the cytoskeleton generates force to deform the cell body, how this force is transduced to the extracellular environment and how the cells are polarized and guided within tissues. To obtain a holistic view of the process we are also studying tissue architecture as well as the distribution and presentation of guidance cues (chemokines) within these tissues. We developed a number of in vitro tools that allow us to observe cytoskeletal dynamics in real time using different life cell imaging approaches. These are all based on advanced light microscopy like total internal reflection, fast confocal and multiphoton technology. We combine these approaches with genetic and pharmacological interference as well as substrate manipulations like surface micropatterning and microfluidics. A general aim of the lab is to test in vitro findings also in the context of living tissues.  To this end we also developed ex vivo (tissue explant) and in vivo imaging setups that allow us to monitor leukocytes together with their physiological environment. Finally we are also interested to test the implications of our findings for physiological immune responses.

Contact
Michael Sixt
Institute of Science and Technology Austria (IST Austria)
Am Campus 1
A – 3400 Klosterneuburg

Phone: +43 (0)2243 9000-3801
E-mail: michael.sixt@remove-this.ist.ac.at

CV and publicaton list

Assistant
Nicole Hotzy

Phone: +43 (0)2243 9000-1032
E-mail: nicole.hotzy@remove-this.ist.ac.at

Team

  • Alexander Eichner, PhD student
  • Maria Frank, Technician
  • Eva Kiermaier, Postdoc
  • Christine Moussion, Postdoc
  • Verena Ruprecht, Joint Postdoc with Heisenberg Group
  • Jan Schwarz, PhD Student
  • Ingrid de Vries, Technician
  • Michele Weber, Postdoc
  • Stefan Wieser, Joint Postdoc with Heisenberg Group

Selected Projects

  • Environmental control of leukocyte migration
    We are investigating how different extracellular constraints like the form of chemokine presentation, mechanical forces and the geometry and molecular composition of the extracellular substrate, affect leukocyte locomotion.
  • Cellular force generation and transduction
    We ask how cytoskeletal activity is translated into actual locomotion. This includes transmembrane force coupling receptors but also locomotion by other means like physical deformation of the cell body.
  • Invasion of tissue barriers
    How do leukocytes traverse tissue boundaries like endothelial / epithelial layers and extracellular matrix

Selected Publications

  • Schumann K, Lämmermann T, Bruckner M, Legler DF, Polleux J, Spatz JP, Schuler G, Förster R, Lutz MB, Sorokin L, Sixt M. Immobilized chemokine fields and soluble chemokine gradients shape migration patterns of dendritic cells. Immunity, 2010 May 28;32(5):703-13
  • Riedl J, Flynn KC, Raducanu A, Gärtner F, Beck G, Bösl M, Bradke F, Massberg S, Aszodi A, Sixt M, Wedlich-Söldner R. Lifeact mice for studying F-actin dynamics. Nat Methods. 2010 Mar;7(3):168-9
  • Pflicke H, Sixt M. Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels. J Exp Med, 2009 Dec 21;206(13):2925-35
  • Renkawitz J, Schumann K, Weber M, Lämmermann T, Pflicke H, Polleux J, Spatz JP, Sixt M. Adaptive force transmission in amoeboid cell migration. Nat Cell Biol, 2009 Dec;11(12):1438-43
  • Lämmermann T, Renkawitz J, Wu X, Brakebusch C, Sixt M. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration. Blood, 2009 Jun 4;113(23):5703-10
  • Lämmermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Söldner R, Hirsch K, Keller M, Förster R, Critchley DR, Fässler R, Sixt M. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature, 2008 May 1;453(7191):51-5
  • Riedl J, Crevenna AH, Kessenbrock K, Yu JH, Neukirchen D, Bista M, Bradke F, Jenne D, Holak TA, Werb Z, Sixt M, Wedlich-Soldner R. Lifeact: a versatile marker to visualize F-actin. Nat Methods, 2008 Jul;5(7):605-7
  • Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt DP, Pabst R, Lutz MB, Sorokin L. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity, 2005 Jan;22(1):19-29

Selected Reviews

  • Nourshargh S, Hordjik P, Sixt M. Regulation of leukocyte motility: through venular walls and beyon. Nat Rev Mol Cell Biol, 2010 May;11(5):366-78
  • Lämmermann T, Sixt M. Mechanical modes of amoeboid cell migration. Curr Opin Cell Biol, 2009 Oct;21(5):636-44
  • Lämmermann T, Sixt M. The microanatomy of T-cell responses. Immunol Rev, 2008 Feb;221:26-43

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