Bionanoscience for Membrane Proteins - Martinez Group

Our group focuses on the investigation of G Protein Coupled Receptors (GPCRs), which are membrane proteins playing an essential role in cell signaling. They mediate a plethora of critical physiological responses involved in numerous regulate numerous physiological processes. It makes them the targets of about 36% of all FDA-approved drugs.


We have a strong interest for the recently identified mechanosensitive properties of GPCRs, which suggest an increasing diversity of activation mechanisms. It opens up a plethora of new questions related to these new mechanisms of activation and the relative importance of mechanical versus chemical cues, which contribute to the tissue specificity of GPCR pharmacology.


Our research is driven by the use of innovative strategies to address this question. We investigate GPCR signaling pathways at the subcellular level in single, living cells with various state-of-the-art fluorescence microscopies and we use small devices and nanomaterials to generate quantitative mechanical cues.

 

 

  • Single cell biophysical studies

  • GPCR signaling at the micro and nanoscale level

  • Use of high-aspect-ratio nanostructures for biological applications

  • Surface sensitive techniques

 

 

 

 

51. Design, synthesis, and time-gated cell imaging of carbon-bridged triangulenium dyes with long fluorescence lifetime and red emission. M. Rosenberg, K.R. Rostgaard, Z. Liao, A.Ø. Madsen, K.L. Martinez, T. Vosch and B.W. Laursen. (2018). Chem. Sci. 

50. Visual Understanding of Light Absorption and Waveguiding in Standing Nanowires with 3D Fluorescence Confocal Microscopy. R. Frederiksen, K.L. Martinez, A. Fontcuberta i Morral and E. Alarcon-Llado. (2017). ACS Photonics. 

49. Rapid Prototyping of Polymeric Nanopillars by 3D Direct Laser Writing for Controlling Cell Behavior. N Buch-Månson, A Spangenberg, LPC Gomez, JP Malval, O. Soppera, K.L. Martinez. (2017). Sci Rep. 

48. Mapping cell behavior across a wide range of vertical silicon nanocolumn densities. N Buch-Månson, DH Kang, D Kim, MH Yoon, K.L. Martinez. (2017). Nanoscale. 

47. Membrane curvature regulates sorting of GPCRs within the plasma membrane of living cells in a ligand-specific manner. KR Rosholm, N Leijnse, A Mantsiou, V. Tkach, SL Pedersen, VF. Wirth, LB Oddershede, KJ Jensen, K.L. Martinez, NS Hatzakis, PM Bendix, A Callan-Jones, D Stamou. (2017). Nature Chem Biology. 

46. Application of nanodisc technology for direct electrochemical investigation of plant cytochrome P450s and their NADPH P450 oxidoreductase. K Bavishi, T. Laursen, K.L. Martinez, B. Lindberg Møller, EA Della Pia. (2016). Sci Rep. 

45. Nanowire-Aperture Probe – Local Enhanced Fluorescence Detection for The Investigation Of Live Cells At The Nanoscale.R. Frederiksen, E. Alarcon-Llado, P. Krogstrup, L. Bojarskaite, N. Buch-Månson, J. Bolinsson, J. Nygård, A. Fontcuberta i Morral and K.L. Martinez. (2016). ACS Photonics. 

44. Functional Stability of the Human Kappa Opioid Receptor Reconstituted in Nanodiscs Revealed by a Time-Resolved Scintillation Proximity Assay. R. Westh Hansen, X.  Wang, A. Golab, O. Bornert, C. Oswald, R. Wagner and K.L. Martinez. (2016). PlosOne. 

43. Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications. S. Vutti, S. Schoffelen, J. Bolinsson, N. Buch-Månson, N. Bovet, J. Nygård, K.L. Martinez and M. Meldal. (2016). Chemistry - A European Journal. 

42. Synthesis of a Polyhistidine-bearing Amphipol and its Use for Immobilizing Membrane Proteins. F. Giusti, P. Kessler, R. Westh Hansen, E.A. Della Pia, C. Le Bon, G. Mourier, J-L  Popot, K.L. Martinez and M. Zoonens. (2015). Biomacromolecules. 

41. Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1) Clustering with MAGUKs Is Mediated via Its C-Terminal PDZ Binding Motif. J. Bender, M. Engeholm, MS Ederer, J. Breu, TC Møller,  S. Michalakis, T. Rasko, EE. Wanker, M. Biel, K.L. Martinez, W. Wurst, JM. Deussing. (2015). PlosOne. 

40. Towards a Better Prediction of Cell Settling on Nanostructure Arrays—Simple Means to Complicated Ends. Buch-Månson, N., Bonde, S., Bolinsson, J., Berthing, T., Nygård, J., Martinez, K.L. (2015). Advanced Functional Materials.

39. Single Domain Antibodies as a Powerful Tool for High Quality Surface Plasmon Resonance Studies. Della Pia, E., Martinez, K.L. (2015). PlosOne.

38. Covalent and stable CuAAC-modification of silicon surfaces for control of cell adhesion. Vutti, S., Buch-Månson, N., Schoffelen, S., Bovet, N., Martinez, K.L., Meldal, M. (2015). Chembiochem.

37. Modulation of fluorescence signals from biomolecules along nanowires due to interaction of light with oriented nanostructures. Frederiksen, R., Alarcon-Llado, E., Madsen, M.H., Rostgaard, K.R., Krogstrup, P., Vosch, T., Nygård, J. Fontcuberta i Morral, A., Martinez, K.L. (2015). Nano Letters.

36. Exploring arrays of vertical one-dimensional nanostructures for cellular investigations. Bonde, S., Buch-Månson, N., Rostgaard, K., Andersen, T. K., Berthing, T., Martinez, K. L. (2014). Nanotechnology.

35. Indium Arsenide nanowire field-effect transistors for pH and biological sensing.Upadhyay, S., Frederiksen, R., Lloret, N., De Vico, L., Krogstrup, P., Jensen, J. H., Martinez, K. L., Nygård, J. (2014). Applied Physics Letters.

34. Functionalized Amphipols: A Versatile Toolbox Suitable for Applications of Membrane Proteins in Synthetic Biology. Della Pia, E. A., Westh Hanse, R., Zoonens, M., Martinez, K. L. (2014). The Journal of Membrane Biology.

33. Synthesis of an oligonucleotide-derivatized amphipol and its use to trap and immobilize membrane proteins. Le Bon, C., Della Pia, E.A., Giusti, F., Lloret, N., Zoonens, M., Martinez, K.L., Popot, J.L. (2014) NAR

32. A Step Closer to Membrane Protein Multiplexed Nano-Arrays Using Biotin-Doped Polypyrrole. Della Pia, E. A., Holm, J. V., Lloret, N., Le Bon, C., Popot, J. L., Zoonens, M., Nygård, J., Martinez, K. L. (2014). ACS Nano.

31. Tuning InAs Nanowire Density for HEK293 Cell Viability, Adhesion, and Morphology: Perspectives for Nanowire-Based Biosensors. Bonde, S., Berthing, T., Madsen, M. H., Andersen, T. K., Buch-Månson, N., Guo, L., Li , X., Badique, F.,  Anselme, K., Nygård, J., Martinez, K. L. (2013).  ACS applied materials & interfaces.

30. Vertical nanowire arrays as a versatile platform for protein detection and analysis. Rostgaard, K. R., Frederiksen, R. S., Liu, Y. C. C., Berthing, T., Madsen, M. H., Holm, J., Nygård, J., Martinez, K. L. (2013). Nanoscale.

29. Active Plasma Membrane P-type H+-ATPase Reconstituted into Nanodiscs Is a Monomer. Justesen BH, Hansen RW, Martens HJ, Theorin L, Palmgren MG, Martinez KL, Pomorski TG, Fuglsang AT. (2013).  Journal of Biological Chemistry, 288(37), 26419-26429.

28. Effects of buffer composition and dilution on nanowire field-effect biosensors. Lloret, N., Frederiksen, R. S., Møller, T. C., Rieben, N. I., Upadhyay, S., De Vico, L., Jensen, H. J., Nygård, J., Martinez, K. L. (2013). Nanotechnology, 24(3), 035501.

27. Identification of a Novel Protein-Protein Interaction Motif Mediating Interaction of GPCR-Associated Sorting Proteins with G Protein-Coupled Receptors. Bornert, O., Møller, T. C., Boeuf, J., Candusso, M. P., Wagner, R., Martinez, K. L., & Simonin, F. (2013). PloS one, 8(2), e56336.

26. PDZ Domain-Mediated Interactions of G Protein-Coupled Receptors with Postsynaptic Density Protein 95: Quantitative Characterization of Interactions. Møller, T. C., Wirth, V. F., Roberts, N. I., Bender, J., Bach, A., Jacky, B. P., Strømgaard, K., Deussing, J. M., Schwartz, T. W.,  Martinez, K. L. (2013). PloS one, 8(5), e63352.

25. A Transparent Nanowire Based Cell Impalement Device Suitable for Detailed Cell–Nanowire Interaction Studies. Mumm, F., Beckwith, K. M., Bonde, S., Martinez, K. L., & Sikorski, P. (2013). Small, 9(2), 263-272.

24. Cell membrane conformation at vertical nanowire array interface revealed by fluorescence imaging. Berthing, T., Bonde, S., Rostgaard, K. R., Madsen, M. H., Sørensen, C. B., Nygård, J., & Martinez, K. L. (2012). Nanotechnology, 23(41), 415102.

23. Intact Mammalian Cell Function on Semiconductor Nanowire Arrays: New Perspectives for Cell Based Biosensing. Berthing, T., Bonde, S., Sørensen, C. B., Utko, P., Nygård, J., & Martinez, K. L. (2011). Small, 7(5), 640-647.

22. "Amphipols From A to Z*" ; J.-L. Popot, T. Althoff, D. Bagnard, J.-L. Catoire, P. Champeil, D. Charvolin, M.J. Cocco, G. Crémel, T. Dahmane, L.M. de la Maza, C. Ebel, F. Gabel, F. Giusti, Y. Gohon, E. Goormaghtigh, E. Guittet, J.H. Kleinschmidt, W. Kuhlbrandt, C. Le Bon, K.L. Martinez, M. Picard, B. Pucci, J.N. Sachs, C. Tribet, C. van Heijenoort, F. Wien, F. Zito and M. Zoonens; Annual Review of Biophysics, 2011, 40, 379-408

21. "Predicting and rationalizing the effect of surface charge distribution and orientation on nano-wire based FET bio-sensors" ; L. De Vico, L. Iversen, M. H. Sørensen, M. Brandbyge, J. Nygård, K. L. Martinez and J.H. Jensen; Nanoscale, 2011, 3(9), 3635-3640.

20. "Quantifying signal changes in nano-wire based biosensors" ; L. De Vico, M. H. Sørensen, L. Iversen, D. M. Rogers, B. S. Sørensen, M. Brandbyge, J. Nygård, K. L. Martinez and J.H. Jensen; Nanoscale, 2011, 3(2), 706-717.
  
19. "Specific and reversible immobilization of histidine-tagged proteins on functionalized silicon nanowires"; Y.-C. Liu, N. Rieben, L. Iversen, B. S. Sørensen, J. Park, J. Nygård and K. L. Martinez; Nanotechnology, 2010, 21(24), 245105, p. 1-8.

18. "Glutamate monitoring in vitro and in vivo: recent progress in the field of glutamate biosensors"; N. Rieben, N. Cherouati and K. L. Martinez ; Journal of Nanoneuroscience, 2009, 1, 1-15.

17. "Chemically specific laser-induced patterning of alkanethiol SAMs : characterization by SEM and AFM"; L. Iversen, O. Younes-Metzler, K. L. Martinez and D. Stamou ; Langmuir, 2009, 25(21):12819-24.

16. "The use of amphipols as universal molecular adapters to immobilize membrane proteins onto solid supports"; D. Charvolin, J.-B. Perez, F. Rouvière, F. Giusti, A. Abdine, K. L. Martinez and J.-L. Popot; PNAS, 2009, 106, p. 405-10.

15. "Applications of nanowire arrays in Nanomedicine"; T. Berthing, C. B. Sørensen, J. Nygård, K.L. Martinez; Journal of Nanoneuroscience. 2008, 1. p. 3-9.

14. "Templated Protein Assembly on Micro-Contact Printed Surface Patterns - Use of the SNAP-tag Protein Functionality"; L. Iversen, N. Cherouati, T. Berthing, D. Stamou and K. L. Martinez; Langmuir. 2008. 24 (12): p. 6375-6381. Click here to see the article.

13. "Ambipolar transistor behavior in p-doped InAs nanowires grown by molecular beam epitaxy"; B.S. Sørensen, M. Aagesen, C.B. Sørensen, P.E. Lindelof, K.L. Martinez and J. Nygård; Applied Physics letters, 2008, 92.

12. "Monitoring the diffusion of Single Heterotrimeric G Proteins in Supported Cell-membrane Sheets Reveals their Partitionning into Microdomains"; J.-B. Perez, J.-M. Segura, D. Abankwa, J. Piguet, K. L. Martinez and H. Vogel; Journal of Molecular Biology. 2006. 363 (5): p. 918-930.

11. "Covalent labeling of cell-surface proteins for in-vivo FRET studies"; B. H. Meyer, K. L. Martinez, J.-M. Segura, R. Hovius, N. George, K. Johnsson and H. Vogel; FEBS Letters. 2006. 580 (6): p. 1654-1658.

10. "FRET imaging reveals that functional neurokinin receptors are monomeric and reside in membrane microdomains"; B. H. Meyer, J.-M. Segura, K. L. Martinez, R. Hovius, N. George, K. Johnsson and H. Vogel; Proc. Nat. Acad. Sci. USA. 2006. 103 (7): p. 2138-2143.

9. "Supported Cell-Membrane Sheets for Functional Fluorescence Imaging of Membrane Proteins"; J.-B. Perez, K. L. Martinez, J.M. Segura and H. Vogel; Advanced Functional Materials. 2006. 16 (2): p. 306-312.


Other Publications:

8. "Reversible Sequential Assays probe Receptor Function in Single Cells"; C. Schreiter, M. Gjoni, R. Hovius, K. L. Martinez, J.-M. Segura and H. Vogel; ChemBiochem. 2005. 6 (12): p. 2187-2194.

7. "Kinetics of the Initial Steps of G Protein-Coupled Receptor Mediated Cellular Signaling revealed by single molecule imaging"; Y. Lill, K. L. Martinez, M. Lill, B. H. Meyer, H. Vogel and B. Hecht; Chemphyschem. 2005. 6(8): p. 1633-1640.

6. "Lipid-coated Nanocrystals as Multi-functionalized Luminescent Scaffolds for Supramolecular Biological Assemblies"; I. Geissbuehler, R. Hovius, K. L. Martinez, M. Adrian, K. R.Thampi and H. Vogel; Angewandte Chemie-International Edition. 2005. 44 (9): p. 1388-1392.

5. "Ligand binding to G-protein coupled receptors in tethered cell membranes"; K. L. Martinez, B. H. Meyer, R. Hovius, K. Lundstrom and H. Vogel; Langmuir. 2003. 19 (26): p. 10925-10929.

4. "Allosteric transitions of Torpedo acetylcholine receptor in lipids, detergent and amphipols: molecular interactions vs. physical constraints"; K. L. Martinez, Y. Gohon, P. J. Corringer, C. Tribet, F. Mérola, J. P. Changeux and J. L. Popot; FEBS letters. 2002. 528 (1-3): p. 251-256.

3. "Structural differences in the two agonist binding sites of the Torpedo nicotinic acetylcholine receptor revealed by time-resolved fluorescence spectroscopy"; K. L. Martinez, P. J. Corringer, S. J. Edelstein, J. P. Changeux and F. Mérola; Biochemistry. 2000. 39 (23): p. 6979-6990.

2. "Experimental autoimmune myasthenia gravis may occur in the context of a polarized T helper(Th)1- or Th2-type immune response in rats"; A. Saoudi, I. Bernard, A Hoedemaekers, B. Cautain, K. Martinez, P. Druet, M. De Baets and J. C. Guéry; Journal of Immunology. 1999. 162 (12): p. 7189-7197.

1. "Polarization toward the T-helper(TH)1 type immune response is not required for rat experimental autoimmune myasthenia gravis"; A. Saoudi, I. Bernard, A Hoedemaekers, B. Cautain, K. Martinez, P. Druet, M. De Baets and J. C. Guéry; Transplantation Proceedings. 1999. 31 (3): p. 1604-1605.

Articles in Popular and Scientific Press:

4."Celler på spid", Weekendavisen, 1st of April 2011

3. "Nanoledninger i celler måler", Ingeniøren, 12th of March 2010

2. Biosensorer, Politiken. 2006. March issue

1. "A study reveals how to better talk to cells"; Press and Information Service of the Swiss Federal Polytechnique School at Lausanne. 2006.

 

 

 

 

 

 

Our research projects are supported by:

Danish Council - Fund for Technology and Innovation

  • CLIPS
  • ANaCell

Danish Council for Independent research – technology and production sciences

  • FTP 11-116984 post-doc grant Sara Bonde

  • FTP 12-132506 post-doc grant Eduardo Della Pia

Danish Council - UNIK

  • UNIK - Synthetic Biology

Danish Council for strategic research

Lundbeck foundation

  • Research projects grants
  • Center for Biomembranes and Nanomedicine: CBN

University of Copenhagen

  • Program of Excellence “BioScaRT”
  • Program of Excellence “Single Molecule Nanoscience”
  • Program of Excellence “bioSYNergy”

Novo Nordisk foundation

  • Exploratory Interdisciplinary Synergy Grant – December 2020
  • GPCR Symposium – October 2019