Personnel
Joachim P. Spatz
University of Heidelberg
joachim.spatz@urz.uni-heidelberg.de
Lab Members:
Tobias Wolfram,
Ferdinand Belz
Research:
Programming cell function by nanoadhesive keys that trigger adhesion mediated cell signaling
The basis of our research is set by a unique nanotechnologial approach, which allows structuring of a gold dotted interface (see Figure 1) with chemical anchors, which are sufficiently small to catch and position single molecules. Proteins, DNA or RNA are potential candidates for being individually located at certain positions at an interface. The nanostructured interface will be functionalized with a variety of proteins and small peptides. This approach is quite powerful since it enables us to test the effect of bioactive molecules presented entirely to the interaction with specific receptors on the cell surface and how lateral positioning of these molecules effects biological functions.
Here, we address a very general phenomenon in cell biology: protein clustering is a general tool to activate higher organized functions. Length scales, which are of importance in receptor-ligand interactions are ideally covered by this nanotechnology. Although clustering is commonly observed in cellular activities, the importance of clustering or the length scales involved are not well known due to the lack of nanotechnological tools.
In cell adhesion, integrin receptors are know to cluster to build-up focal adhesion sites. We have demonstrated that activation and separation of single integrins by more than 73 nm results in fatal failure of cell adhesion, while separations of integrins up to 58 nm allows formation of well focal adhesion sites.
Programming cell function by nanoadhesive keys that trigger adhesion-mediated cell signaling and cell differentiation. Cell-Extracellular Matrix (ECM) interactions are complex, highly regulated processes that play a crucial role in most fundamental cellular functions including motility, proliferation, differentiation and apoptosis. Focal adhesions and related structures are major cellular sites responsible for cell-ECM attachment and adhesion-mediated signaling. These complex supermolecular structures consist of transmembrane integrin receptors linked to the actin cytoskeleton via cytoplasmic anchor proteins, such as vinculin, paxillin and focal adhesion kinase.iv. Integrins are heterodimers formed by non-covalent association of and subunits that bind to a RGD (Arginine-Glycine-Aspatate) motif, a sequence present in many ECM proteins. It had been shown that assembly of the molecular complexes at focal adhesion sites requires both occupancy and clustering of the integrin receptors, though the molecular properties of these clusters have not been defined.
Cell-Cell interactions are playing also decisive roles in cellular functions including cell proliferation, differentiation and cell survival. Proteins such as members of the Immunglobulin-Superfamily and members of Cadherin-Family are known to mediate most of these functions. To investigate cellular differentiation we are using not only proteins of cell adhesion families, but also differentiation factors such as agrin in association with Rob Burgess, TJL. We are utilizing our nanotechnology based approach to address the general question, how we can influence cellular behaviour resulting in specific adhesion and differentiation properties of the cell on the structured surface. In general we have a neurobiological focus using different proneural and neuron-like cell lines (figure 3) as well as primary neurons from mice.
A successful approach for programming cell functions by the positioning of single molecules requires a rather perfectly ordered array of bioactive anchor groups on a stiff template. The rigidity of the template is essential since it dictates the cell where to located transmembrane proteins. The nanostructured surface may be functionalized by small peptides such as RGD, or whole extracellular domains of proteins such as Agrin or Cadherins. The perfectly controlled chemical environment and the spacing of these bioactive molecules in a nanometer range enables us to investigate different biological functions on a cellular level with a high selectivity. The long range applications of this research may lead to improvements in transplant medicine and tissue engineering, where there is an great demand for specifically designed surfaces.
Recent Publications:
Roos W, Roth A, Sackmann E, Spatz JP. 2003. Freely suspended actin cortex models on arrays of mirco-fabricated pillars. Chem Phys Chem 4:872-877
Micoulet A, Beil M, Wichert GV, Paschke S, Walter P, Omary MB, Van Veldhoven PP, Gern U, Wolff-Hieber E, Eggermann J, Waltenberger J, Adler G, Seufferlien T, Spatz JP. 2003. Sphingosylphosphorylocoline regulates the keratin network architecture and the visocelastic properties of human epithelial tumour cells. Nat Cell Bio 5:803-811
Spatz JP. 2003. Cell – Nanostructure interactions. In: Nanobiotechnology. Wiley-VCH, Weinheim. 53-65
Kemkemer R, Schrank S, Gruler H, Kaufmann D, Spatz JP. 2004. Process of cell shape normalization of normal and haploinsufficient NF1-melanocytes through substrate interaction. Chem Phys Chem 1:85-92
Arnold M, Cavalcanti-Adam A, Glass R, Blummel J, Eck W, Kessler H, Spatz JP. 2004. Activation of integrin function by nanopatterned adhesive interfaces. Chem Phys Chem 3:383-388
Park C-W, Knemeyer J-P, Marme N, Moller M, Spatz JP, Wolfrum J, Sauer M. 2004. Accurate delivery of single biomolecules by polyethylene glycol coated submicrometer pipettes. Chem Phys 301:105-110
Moller M, Hartmann Ch, Sihler J, Fricker S, Chan VZH, Spatz JP. 2004. Ordering and packing periodicity of Au-containing block copolymer miscelles. Polym Mat Sci Eng 90:255-256
Glass R, Arnold M, Cavalcanti-Adam EA, Blummel J, Haferkemper C, Dodd C, Spatz JP. 2004. Block copolymer micelle nanolithography on non-conductive substrates. New J Phys 6:101
Schmitz CHJ, Curtis JE, Spatz JP. 2004. Constructing and probing biomimetic models of the actin cortex with holographic optical tweezers. SPIE 5514:446-454
Curtis JE, Spatz JP. 2004. Getting a grip: Hyaluronan-mediated cellular adhesion. SPIE 5514:455-466
Zimerman B, Arnold M, Ulmer J, Blummel J, Besser A, Spatz JP, Geiger B. 2004. Formation of focal adhesion-stress fibre complexes coordinated by adhesive and non-adhesive surface domains. IEE Proc Nanobiotechnol 151:62-66
Suresh S, Spatz JP, Mills JP, Micoulet A, Dao M, Lim CT, Beil M, Seufferlein T. 2005. Acta Biomaterialia 1:15-30
Micoulet A, Ott A, Spatz JP. 2005. Mechanical response analysis and power generation by single-cell stretching. Chem Phys Chem 6:663-670
Curtis JE, Schmitz CH, Spatz JP. 2005. Symmetry dependence of holograms for optical trapping. Optics Let 30:2086-2088
Spatz JP. 2005. Building up micromuscles. Nat Mat 4:115-116
Marme N, Weston KD, Staudt T, Spatz J, Knemeyer J-P. 2005. A fluorescence-based assay for exopeptidases using self-quenching peptide probes with single-molecule sensitivity. Intern J Environ Anal Chem 85:741-751
Groll J, Ameringer T, Spatz JP, Moller M. 2005. Ultrathin coatings from isocyanate-terminated star PEG prepolymers: Layer formation and characterization. Langmuir 21:1991-1999
Kastle G, Schroder A, Boyen H-G, Plettl A, Ziemann P, Mayer O, Spatz J, Moller M, Buttner M, Oelhafen P. 2005. Electrical resistivity of epitaxial Au films surface-modulated by arrays of Pt nanoparticles. Eur J Inorg Chem 3691-3698
Brucker Ch, Spatz J, Schroder W. 2005. Feasability study of wall shear stress imaging using microstructured surfaces with flexible micropillars. Exp Fluids 39:464-474
Schmitz CHJ, Curtis JE, Spatz JP. 2005. High-precision steering of multiple holographic optical traps. Optics Express 12:8676-8685
Cavalcanti-Adam EA, Micoulet A, Blummel J, Auernheimer J, Kessler H, Spatz JP. 2005. Lateral spacing of integrin ligands influences cell spreading and focal adhesion assembly. Eur J Cell Bio, (in press)
Roos W, Ulmer J, Surrey T, Spatz JP. 2005. Microtubule gliding and crosslinked microtubule networks on micro-pillar interfaces. Nano Let, (submitted)
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