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Cell Biology, Biophysics: Membrane Trafficking, Membrane-cytoskeleton interaction, Cell migration
Dr Nils Gauthier joined the Mechanobiology Institute as a Senior Research Fellow in November 2010 after a Postdoctoral work in Pr Michael Sheetz Lab at Columbia University, New York, USA. His postdoctoral work focused on membrane dynamics and membrane cytoskeleton interactions during cell motility. He did his Ph.D in Pr Patrice Boquet Lab, at the University of Nice-Sophia-Antipolis, Nice, France. His work concentrated on the endocytosis and intra-cellular trafficking of the Helicobacter Pylori VacA cytotoxin, the bacterial pathogen H.p. being the major cause for gastric ulcers and a high risk factor for gastric cancers. His past experiences let him approache different fields of Biology like Cellular-Microbiology, Host-pathogen Interactions, Endocytosis, Membrane Trafficking and Membrane Dynamics, Exocytosis, Cytoskeleton Dynamics, Cell Division and Migration.
Plasma membrane tension orchestrates membrane trafficking, cytoskeletal remodeling, and biochemical signaling during phagocytosis
Thomas A. Masters, Virgile Viasnoff, You Li and Nils Gauthier* Proc Natl Acad Sci USA 2013.
* Corresponding author
Model for pseudopod extension: After bead engagement (i) PIP3-Rac1 signaling is activated and actin polymerization pushes the pseudopod membrane forward around the particle during the first phase (ii). Membrane tension is higher than prior engagement because of protrusion, leading to membrane buffer (folds) depletion. At the transition (iii), a spike in membrane tension due to competition between membrane area depletion and protrusive activity leads to PIP3-Rac1 deactivation and actin reorganization in the pseudopod as well as exocytosis activation. In the second phase (iv) of pseudopod extension, membrane area is increased by an actin associated exocytosis of GPI-anchored protein containing vesicles. Particle internalization is initiated and pseudopodia extension progressively wraps the particle as it enters the cell body. After engulfment, (v), maturation is initiated and subsequently involves lysosome fusion and potentially Golgi and ER compartments.
Adesion maturation through force-dependent α-actinin competition with talin
Pere Roca-Cusachs, Armando del Rio, Eileen Faucher, Nils C. Gauthier, Nicolas Biais, Michael P. Sheetz. Proc Natl Acad Sci USA 2013.
Mechanical Feedback between Membrane Tension and Dynamics
Nils C. Gauthier*, Thomas M. Masters, Michael P. Sheetz. Trends in Cell Biology, 2012.
* Corresponding author
Model of cell spreading and polarization a) Round up cell with only weak cell-substrate attachment but higher membrane tension than interphase cell (2 to 3 fold) (e). Membrane folds are clearly visibles at this stage (see also Fig. 1 panel a). b) Rapid and non-contractile phase of spreading where unfolding of the membrane reservoirs provides extra membrane area. In this phase, membrane tension is at a high but constant level compared to interphase cell. c) Spreading phase transition with entry into the contractile spreading phase or P2. The membrane reservoirs are totally unfolded and give rise to an increase in membrane tension due to area limitation. This is followed almost immediately by activation of exocytosis and Myosin II mediated contraction. d) As the cell progress into P2, the leading edge becomes more heterogeneous with alternating of protrusive and retractile regions along the boundary. Stable adhesion start to mature at that stage due to contaction activation and a global remodeling of the cytoskeleton occurs with formation of actin bundles. The cell starts to exert strong forces onto the substrate at this point. As a consequence of exocytosis and further spreading, the membrane area progressively increase whereas membrane tension progressively decreases. e) The cell is now fully spread and presents a drastic reduction in protrusive-retractive activities while actin bundles have matured into strong and clearly identifiable stress fibers linking focal adhesions. The membrane tension is now at its low resting level with endocytosis and exocytosis balance maintaining a constant membrane area. f) P3, or the polarized phase. As a consequence, lamellipodia protrude on one side of the cell while the other side of the cell shrinks. Due to protrusion, membrane tension increase and the higher tension seems to help to maintain polarity .
Physarum polycephalum percolation as a paradigm for topological phase transitions in transportation networks
Adrian Fessel, Christina Oettmeier, Erik Bernitt, Nils C. Gauthier, Hans-Günther Döbereiner. Physical Review Letter, 2012.
– Cover featured August 17
– Science News reviewed August 2012
Easy fabrication of thin membranes with through holes. Application to protein patterning
Thomas Masters, Wilfried Engl, Zhe Lancelot Weng, Bakya Ashwin, Nils C. Gauthier, Virgile Viasnoff. PLOS ONE, 2012.
Cell crawling mediates collective cell migration to close undamaged epithelial gaps
Ester Anon, Xavier Serra-Picamal, Pascal Hersen, Nils C. Gauthier, Michael P. Sheetz, Xavier Trepat, Benoit Ladoux. Proc Natl Acad Sci USA 2012.
Temporary Increase in Plasma Membrane Tension Coordinates the Activation of Exocytosis and Contraction during Cell Spreading
Gauthier N.C., Fardin M.A., Roca-Cusachs P., and Sheetz M.P. Proc Natl Acad Sci USA 2011 Aug 30, 14467-72.
– Faculty of 1000 evaluated: FFa10, 2 evaluations
– Cover Featured in the August 30 2011 issue of PNAS
– Commented in the August 30 2011 issue of PNAS by Kinneret Keren:
– Membrane tension leads the way, Proc Natl Acad Sci USA 2011 Aug 30, 14379-80
Physiological response to membrane protein overexpression in E. coli.
Gubellini F, Verdon G, Karpowich NK, Luff JD, Boel G, Gauthier N, Handelman SK, Ades S, Hunt JF. Mol Cell Proteomics. 2011 Jun 30.
Bacillus sphaericus binary toxin elicits host cell autophagy as a response to intoxication
Opota O, Gauthier NC, Doye A, Berry C, Gounon P, Lemichez E, Pauron D. PLoS One. 2011 Feb 14;6(2):e14682.
Filamin depletion blocks endoplasmic spreading and destabilizes force-bearing adhesions
Lynch CD, Gauthier NC, Biais N, Lazar AM, Roca-Cusachs P, Yu CH, Sheetz MP. Mol Biol Cell. 2011 Apr;22(8):1263-73.
– Faculty of 1000 : poster selected ASCB meeting 2009
Cell spreading as a hydrodynamic process
Fardin MA, Rossier OM , Rangamani P, Avigan PD , Gauthier NC , Vonnegut W , Mathur A , Hone J , Iyengar R , Sheetz MP. Soft Matter 2010 Volume: 6 Issue: 19 Pages: 4788-4799.
Force generated by actomyosin contraction builds bridges between adhesive contacts
Rossier OM, Gauthier N, Biais N, Vonnegut W, Fardin MA, Avigan P, Heller ER, Mathur A, Ghassemi S, Koeckert MS, Hone JC, Sheetz MP. EMBO J. 2010 Feb 11.
Cytoskeletal coherence requires myosin-IIA contractility
Cai Y, Rossier O, Gauthier NC, Biais N, Fardin MA, Zhang X, Miller LW, Ladoux B, Cornish VW, Sheetz MP. J Cell Sci. 2010 Feb 1;123(Pt 3):413-23.
Plasma membrane area increases with spread area by exocytosis of a GPI-anchored protein compartment
Gauthier NC, Rossier OM, Mathur A, Hone JC, Sheetz MP. Mol Biol Cell. 2009 Jul;20(14):3261-72. Incytes from MBC July, Vol 20.
– Cover caption of the October 15
– 2009 issue of MBoC
Clustering of alpha(5)beta(1) integrins determines adhesion strength whereas alpha(v)beta(3) and talin enable mechanotransduction
Roca-Cusachs P, Gauthier NC, Del Rio A, Sheetz MP. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16245-50. Faculty of 1000 evaluated : FFa9 : 2 evaluations
Early endosomes associated with dynamic F-actin structures are required for late trafficking of H. pylori VacA toxin
Gauthier NC, Monzo P, Gonzalez T, Doye A, Oldani A, Gounon P, Ricci V, Cormont M, Boquet P. J Cell Biol. 2007 Apr 23;177(2):343-54.
Helicobacter pylori VacA toxin: a tool to study novel early endosomes
Gauthier NC, Ricci V, Landraud L, Boquet P. Trends in Microbiology. 2006 Jul;14(7):292-4.
Helicobacter pylori VacA cytotoxin: a probe for a clathrin-independent and Cdc42-dependent pinocytic pathway routed to late endosomes
Gauthier NC, Monzo P, Kaddai V, Doye A, Ricci V, Boquet P. Mol Biol Cell. 2005 Oct;16(10):4852-66.
Glycosylphosphatidylinositol-anchored proteins and actin cytoskeleton modulate chloride transport by channels formed by the Helicobacter pylori vacuolating cytotoxin VacA in HeLa cells
Gauthier NC, Ricci V, Gounon P, Doye A, Tauc M, Poujeol P, Boquet P. J Biol Chem. 2004 Mar 5;279(10):9481-9.
Gastric cell apoptosis and H. pylori: has the main function of VacA finally been identified?
Boquet P, Ricci V, Galmiche A, Gauthier NC. Trends in Microbiology. 2003 Sep;11(9):410-3.