Lena Lautscham


Lena

 

 

 

 

 

 

 

 

 

 

 

 

 

PhD student

Room 02.073

Center for Medical Physics and Technology
Biophysics Group
Henkestrasse 91
91052 Erlangen
Germany

tel : (+49) (0)9131-85-25602;
fax: (+49) (0)9131-85-25601
email: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Projects

 

'Migration through narrow channels: How cancer cells evade the steric hindrance of a 3D matrix.'

To metastasis, cancer cells need to migrate through  the extracellular matrix. In this 3 dimensional environment their migration is sterically hindered by small pores. It is currently unknown how the pore size influences migration speed. We use a microfluidic device to investigate cell migration through narrow channels. Channels are fabricated in polydimethylsiloxane rubber using soft lithography. A series of 15 channel segments (20 µm length, 3.7 µm height, with a decreasing width from 10 to 1.7 µm) are separated by 20x20µm chambers so that cells can spread and relax between channel crossings. For channels narrower than 9 µm, the nucleus of both cell lines undergoes considerable elongation. Surprisingly, nuclear speed increases in narrower channels. Moreover, nuclear speed is higher within the channel compared to within the chamber. However, if the overall height of both channel and chamber is increased from 3.7 to 7.4 µm, the migration speed also increases. These data, taken together, are consistent with the notion that the deformability of the cell nucleus is the limiting factor during migration through narrow openings. As the nucleus becomes wedged against the channel entrance, the cell builds up tractions to deform the nucleus. This process requires strong adhesions. Once fully deformed, the nucleus glides through the channel with less resistance and thus higher speed. By this mechanism, the cell can dramatically lower the resistance posed by narrow pores and thereby maintain a high speed even in the presence of high steric hindrance.

channel lena 

Figure 1: (A) Channel structure with invaded breasts cancer cells, nucleus stained with Hoechst (red). Channel width gradually decreases from 11.2 μm (left) μm to 1.7 μm (right). (B) Kymograph of a cell transmigrating through a 1.7μm wide channel. (C) Average nucleus velocity across large, medium and small channels, for HT1080 fibrosarcoma cells (n=53), MDA-MB-231 breast carcinoma cells (n=78), A125 lung carcinoma cells (n=64), and PS primary breast carcinoma cells (n=26).

 

 

'Mechanosensitiv signal transduction of cells on adhesive lipid bilayers'

Cell adhesion and cell-cell contacts critically influence cell metabolism, protein synthesis, cell survival, cytoskeletal architecture, and consequently cell mechanical properties like migration, spreading, and contraction. A major determinant for cellular behavior is the mechanical environment, and current thinking suggests that the dynamic interplay between cell tractions and substrate deformation is key for the understanding of mechano-sensing. While previous studies focused on substrate elasticity to investigate cellular mechano-sensing and -transduction, we use a new biomembrane-mimicking substrate with distinct material properties as an alternative route to probe the influence of matrix mechanics on cellular response. These substrates are developed by our collaborators in Indianapolis (Christoph Naumann, IUPUI Department of Chemistry and Chemical Biology). The substrates consists of a polymer-tethered multi-lipid bilayers on a solid support, they exhibits a viscous response with respect to individual linkers and a rather elasto-plastic response in the presence of linker clusters. In contrast to elastic substrates where deformations come to a halt when cell tractions reach steady state, cell adhesions in viscous substrates remain mobile and thus provide a different mechanical stimulus.

 

Bilayer traction 

Figure2: (A) Diagram of the stacked bilayer substrate. With growing distance from solid support, linker mobility increases.  (B) Bright field image of MEF cells on PAA gel, triple bilayer and (C) their corresponding traction fields.

Experimental techniques

 

cell motility tracking, Image analysis, 2D-traction microscopy, video particle tracking, magnetic tweezers, protein labelling, TIRF imaging,  confocal imaging, optical tweezers

 

 

Curriculum Vitae

since 2010 PhD student at LPMT Uni Erlangen, fellow of the IMPRS Erlangen (MPI for the science of light)
2008-2010 Diplomathesis with Prof. Christoph F. Schmidt at Drittes Physikalisches Institut-Biophysik Uni Göttingen
  Thesis title:'Mechanics of differentiating pluripotent mouse cells - active and passive cell microrheology
2007-2008 ERASMUS at Universitat degli Studi di Padova, Padua, Italien
2006 Vordiplom in physics at Georg-August Universität, Göttingen
2004-2010 study in physics at Georg-August Universität, Göttingen
2004 Abitur at Otto-Hahn-Gymnasium, Göttingen
2002 High School Diploma at Union Pines High School, Carthage, North Carolina, USA
  Participation at regional science fair Department of Chemistry and Physics, University of North Carolina
2001-2002 Exchange year in North Carolina, USA

 

Awards and Funding

2010-2013 Funded by IMPRS
2011 Best Junior Speakers Award, Cell Mech 2011
2010 Förderbeitrag der Wilhelm und Else Heraeus-Stiftung, DPG 2010

 

Conferences

2013 5th European Cell Mechanics Meeting, Obergurgle Austria (Poster:'Mechanosensing of cells on biomembrane-

        mimicking substrates')

        ASCB, New Orleans (Poster:'Migration through narrow channels:How cancer cells evade the steric hindrance of

         a 3D matrix.')

 2012 DPG Tagung, Berlin (Talk:' Viscosity-Sensing and Mechano-Transduction of Cells on Adhesive Lipid Bilayers')

 4th International Symposium Interface Biology of Implants (IBI) 2012, Warnemünde (Talk:' Mechano-sensing of cells on viscous biomembrane-mimicking substrates')

2011 4th European Cell Mechanics Meeting, Amsterdam (Talk: 'Viscosity-Sensing and Mechano-Transduction in Mouse Embryonic         Fibroblasts on  Adhesive Lipid Bilayers')

2010 DPG Tagung, Regensburg (Talk: ' Probing mechanical characteristics of differentiating pluripotent mouse stem cells')

2009 DPG Tagung, Dresden

 

Publications

  • 2014

      Biomembrane-mimicking lipid bilayer system as a mechanically tunable substrate

        Biomaterials 35  3109-3207, 2014

      Lautscham L.A., Lin C.Y., Auernheimer V., Naumann C.A., Goldmann W.H. and Fabry B.
                       

  • 2013

CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics

Cellular and Molecular Life Sciences (2013); doi: 10.1007/s00018-013-1450-x
R. Janoštiak, J.Brábek,V. Auernheimer, Z.Tatárová, L.A.Lautscham, T. Dey, J.Gemperle,R.Merkel,W. H.Goldmann, B.Fabry, D. Röse
 
Differential interference contrast microscopy using light-emitting diode illumination in conjunction with dual optical traps
Rev. Sci. Instrum. 84, 053703 (2013); doi: 10.1063/1.4804597
C. Battle, L. Lautscham, and C. F. Schmidt
 
Identification of DAPK as a scaffold protein for the LIMK/cofilin complex in TNF-induced apoptosis
The International Journal of Biochemistry & Cell Biology 
Ivanovska, J, Tregubova, A , Mahadevan, V, Chakilam, S, Gandesiri, M, Benderska, N, Ettle, B, Hartmann, A, Söder, S, Ziesché, E, Fischer, T, Lautscham, L, Fabry, B, Segerer, G, Gohla, A, Schneider-Stock, R
 
  • 2012

 Biomechanical characterization of a desminopathy in primary human myoblasts

Biochem Biophys Res Commun. 2012 Mar 23;419(4):703-7. PMID: 22386993

Bonakdar N, Luczak J, Lautscham L, Czonstke M, Koch TM, Mainka A, Jungbauer T, Goldmann WH, Schröder R, Fabry B.

 

Cellular Mechano-Stimulation by Adjusting the Viscous Drag of Cell-Substrate Linkers in Biomembrane-Mimicking Cell Substrates

Biophysical Journal, Volume 102, Issue 3, 565a, 31 January 2012

Yu-Hung Lin, Daniel E. Minner, Lena Lautscham, Andreas Schoenborn, Wolfgang Goldmann, Ben Fabry and Christoph A. NaumannVolume

 

  • 2011
 
Inhibition of Rho kinases increases directional motility of microvascular endothelial cells


Biochemical Pharmacology, Volume 83, Issue 5, 1 March 2012, Pages 616-626
Johannes Breyer, Jana Samarin, Margot Rehm, Lena Lautscham, Ben Fabry, Margarete Goppelt-Struebe