Nadine Lang

Nadine Lang

NadineL2012

PhD student

Room 02.073

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

tel : (+49) (0)9131-85-25612;
fax: (+49) (0)9131-85-25601
email: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

 

Projects

Phd Thesis : Migration dynamics of tumor cell lines through dense 3D collagen networks


Effects of matrix stiffness and steric hindrance on cell migration in 3D

The process of cell migration in a porous 3-dimensional (3-D) connective tissue is of crucial importance for establishing proper organ function and metastasis building. Studies performed on flat 2-D surfaces revealed that cell migration strongly depends on matrix stiffness. Whether this holds true also in a 3-D porous structure is currently unclear. Here we use self-assembled collagen biopolymer networks as matrices. By varying the collagen concentration from 0.3 to 2.4 mg/ml, we achieve pore sizes between 3 to 8 µm, resembling the connective tissue matrix of organs. To increase the stiffness of the network (~2-fold) without altering collagen concentration and pore size, we added glutaraldehyde (GA) as a crosslinker. Toxic unbound aldehyde groups were removed by extensive washing with TRIS buffer. Cell migration into the matrix was studied by adding MDA-MB-231 onto the surface of collagen gels. After 3 days of culture, the cell density as a function of invasion depth was measured. Migration in the 0.3 and 0.6 mg/ml collagen gels (8 µm and 5 µm pores) was drastically enhanced after the gels were stiffened with GA. By contrast, migration in 2.4 mg/ml collagen (3 µm pores) gels was drastically reduced after the gels were stiffened with GA. Live cell imaging over 24h revealed super-diffusive and persistent migration behavior in all gels, but cells in medium-density gels migrated faster than cells in dense gels. These results demonstrate that 3-D cell migration is enhanced by higher matrix stiffness but only as long as the pore size does not fall below a critical value where it causes excessive steric hindrance.

 

Estimating the true 3D pore size distribution of biopolymer networks from directionally biased data

 

The pore size of biopolymer networks governs their mechanical and functional properties. Confocal reflection microscopy or second harmonic generation microscopy are widely used to image biopolymer networks, however, both techniques fail to resolve vertically oriented fibers. We describe how to recover the true pore size of biopolymer networks from such directionally biased data. We first determine the distribution of distances from random points in the fluid phase to the nearest fiber. This distribution follows a Rayleigh distribution, regardless of isotropy and data bias. A Rayleigh distribution is fully described by a single parameter - the characteristic pore size of the network. We show that a biased pore size can be converted to the true pore size simply by multiplication with the square root of the visible network fraction. We experimentally verify the validity of our approach by comparison with data obtained using confocal fluorescence microscopy, which represents the full structure of the network. As an important application, we investigate the pore size dependence of self-assembled collagen networks on protein concentration. We find that the pore size decreases with the square root of the collagen concentration, consistent with a total fiber length that scales linearly with the monomer concentration.

 

 

 

 

Curriculum Vitae

University

since 03/2010   

PhD Student at Lehrstuhl für physikalisch-medizinische Technik, Friedrich Alexander Universität Erlangen (FAU)

Title: Migration dynamics of tumor cell lines through dense 3D collagen networks

10/2008-01/2010      

Diploma thesis at Lehrstuhl für physikalisch-medizinische Technik, FAU

Title: A combined setup for FCS and FRAP on a budget

06/2009-09/2009 Research project at McGill University in Montreal, Canada
10/2006-10/2008 Hauptstudium Physics at FAU with focus on physics in medicine
09/2006-02/2007 Erasmuns semester at Université Lille I - Sciences et Technologies, Lille, Frankreich
10/2004-10/2006 Grundstudium Physics at Friedrich Alexander Universität Erlangen

 

School

 

09/2002-05/2004       
Sigmund-Schuckert-Gymnasium Nürnberg, Abitur
09/2001-07/2002 Helene-Lange-Gymnasium Fürth
09/2000-07/2001  Übergangsklasse am Holbein Gymnasium Augsburg
09/1997-05/2000 Dr. Max Josef Metzger Realschule Meitingen, Realschulabschluss
09/1991-07/1997 Grund-und Hauptschule Biberbach

 

Languages

 

German                        
native speaker
English fluent
French fluent (DELF/DALF - Level B2)
Spanish           advanced (Unicert II)           

 

Awards, Scholarships and Funding

09/2013  Award for best young scientist's talk at the Annual Meeting of the Society for Biomaterials
   
12/2011 Funding from Department of Gender Diversity for  Annual Meeting of American Society for Cell Biology, Denver,USA                                                                                          
03/2010                
Funding from Wilhelm and Else Heraeus foundation for DPG Frühjahrstagung, Regensburg
06/2009 Scholarship from Department of gender diversity FAU for research project in Montreal,Canada
06/2009 Funding from BaCaTech for research project in Montreal, Canada               
03/2009 Funding from Wilhelm and Else Heraeus foundation for DPG Frühjahrstagung, Dresden
09/2006-02/2007 Scholarship from Erasmus program for semester abroad in France
03/2001 Scholarship Oscar Karl Forster
05/2000 Graduated Best in Class and Region, Landkreis Augsburg

 

Conferences

First Author

 

09/2013

20th Annual Meeting 'Deutsche Gesellschaft für Biomaterialien', Erlangen

Talk and Poster„Effects of matrix stiffness and steric hindrance on 3D cell migration“

Authors: Nadine Lang, K.Skodzek, S. Hurst, A.Mainka, B.Fabry

06/2013                  

5th scientifc seminar of the northbavarian biomaterials alliance (NBBA), Würzburg  

Rapid Talk and Poster: „Effects of matrix stiffness and steric hindrance on 3D cell migration“  

Authors: Nadine Lang, K.Skodzek, S. Hurst, A.Mainka, B.Fabry

11/2012

Annual meeting 'Deutsche Gesellschaft für Biomaterialien', Hamburg  

Section Talk: „Cells respond to matrix stiffness during 3D migration through dense collagen networks“

Authors: Nadine Lang, S.Münster, K.Skodzek, A.Mainka, B.Fabry

12/2011

Annual Meeting of American Society for Cell Bioloy, Denver, Colorado,USA

Poster: „ Extracting pore size statistics of collagen gels from 3D confocal image stacks"

Authors: Nadine Lang, J.Lange, P.Krauss, C.Metzner, B.Fabry    

Poster„ Transfection can impair cell migration and mechanical cell behaviour“                  

Authors: Nadine Lang, A. Mainka, N.Bonakdar, W.Goldmann,

09/2011

4th European Cell Mechnics Meeting, Amsterdam, Netherlands

Poster: „ Transfection can impair cell migration and mechnical cell behaviour“

Authors: Nadine Lang, A. Mainka, N.Bonakdar, W.Goldmann, B.Fabry

03/2010

Annual meeting ' Deutschen physikalische Gesellschaft', Regensburg  

Poster: „Vinculin lipid anchorage infuences focal adhesion strength and turnover“ 

 Authors: Nadine Lang,G.Diez, W.Goldmann, B.Fabry

02/2010

 Annual Meeting of Biophysical Society, San Francisco, California, USA

Poster: „Vinculin lipid anchorage infuences focal adhesion strength and turnover“

Authors: Nadine Lang,G.Diez, W.Goldmann, B.Fabry

03/2009

Annual meeting ' Deutschen physikalische Gesellschaft', Dresden

Section Talk: „Vinculin lipid anchorage influences focal adhesion strength and turnover“

 

Authors: Nadine Lang,G.Diez, W.Goldmann, B.Fabry

 

 

Co-Author

11/2012                   

3rd Meeting Physics of Cancer, Leipzig

Poster:   Mechanics of Collagen Gels - What cells feel  

Authors: J.Steinwachs, C.Metzner, N.Lang, S. Münster, B.Fabry

03/2012

Annual meeting ' Deutschen physikalische Gesellschaft', Berlin

Talk: Reconstruction of Cellular Forces during Migration through Non-Linear and Non-Affine Collagen Networks

Authors: J. Steinwachs, C. Metzner, N. Lang, N. Bonakdar, S. Münster, B. Fabry 

02/2012 

Biophysical Society 56th Annual Meeting (San Diego)

Talk: Estimation of Cellular Forces during Migration through Non-Linear and Non-Affine Collagen Networks

Authors: J. Steinwachs, C. Metzner, N. Lang, N. Bonakdar, S. Münster, B. Fabry

03/2009

Annual meeting ' Deutschen physikalische Gesellschaft', Dresden

Poster: Design of a low-cost modular FCS, FRAP and Optical Tweezers setup for educational use

Authors: T.Bloem, Nadine Lang, P.Kollmannsberger, B.Fabry

 

 


Publications

 

2014

 

 

Lang N.R., Skodzek K., Hurst S., Mainka A., Steinwachs J., Schneider J, Aifanits K.  and Fabry B.

Biphasic response of cell invasion to matrix stiffness in 3-dimensional biopolymer networks

Acta Biomaterialia (accepted, November 2014)

 

 

R.Buslei,P.Strissel, C.Henke, R.Schey, Nadine Lang, M.Ruebner, C.C. Stolt, B.Fabry, R.Strick

Activation and regulation of endogenous retroviral genes in the human pituitary gland related endocrine tumors

Neuropathology and Applied Neurobiology (March  2014)

 

2013

Nadine Lang, S.Münster, C.Metzner, P.Krauss, J.Lange, S.Schürmann, K.E.Aifantis, O.Friedrich and Ben Fabry

Estimating the 3D pore size distribution of biopolymer networks from directionally biased data

Biophysical Journal (Nov 2013)

2012                              

C.Henke, M. Ruebner, F.Faschingbauer, C.C.Stolt, N. Schaefer, Nadine Lang, M.W.Beckmann, P.L.Strissel, R.Strick

Regulation of murine placentogenisis by the retroviral genes Syncetin-A, Syncetin-B and Peg10

Differentiation (accepted Feb 2013)

2012

Krauss P., Metzner C., Lange J., Nadine Lang, Fabry B.

Parameter- Free Binarization and Skeletonization of Fiber Networks from Confocal Image Stacks

PloS ONE 7:e36575, 2012  

2010           

Küpper K., Nadine Lang, Möhl C., Kirchgeßner N., Born S., Goldmann W.H., Merkel R., Hoffmann B.

Tyrosine phosphorylation of vinculin at position 1065 modi"es focal adhesion dynamics and cell tractions

Biochem Biophys Res Commun 399:560-564, 2010