Prof. Dr. med. Richard H.W. Funk
Project "Physical factors influencing the cell"
Coming from the experiments with light, infrared, temperature, electromagnetic fields (EMF) [3]), we (Dr. Özkuzur, S. Perikhe, J. Derix and Prof. Monsees now University of Kapstadt, South Africa) tried to find guidance and adhesion cues (e.g. to probe and construct implant surfaces [2, 4, 6]) in different cell types especially osteoblasts. To our great surprise we found that one of the most important cues for guiding cell adhesion are electric charges on the implant surface as well as the ionic composition in the medium between the cell and the surface [8].
Regarding ions and charges, a general change in paradigm took place concerning the endogenously produced static electric fields (EF) of cells and tissues [3, 5]. Now, the action of ion transporters and ion channels could be linked to the ‘‘electric’’ action of cells and tissues. Also, sensing of these ion gradients was demonstrated in studies of cell migration and wound healing. Furthermore, the triggers exerted by ion concentrations and concomitant electric field gradients have been traced along signalling cascades till gene expression changes. Interestingly, changes in ion concentrating can also be transmitted by real newly detected "tunneling nanotubes" [10].
We could also reveal that the pattern of NHE3 and Na/K ATPase accumulations on leading edges of the cells during EF-directed migration resemble to filopodia and focal adhesions, respectively [8]. Thus we suggest that there might be interactions between NHE3 and Na/K ATPase and cytoskeletal proteins related to these patterns such as ß actin (locates in the leading edge of migrating cells) and vinculin (important protein for adhesion turnover) [8, 9].
In tail regeneration studies in the axolotl model we could reveal a sequential activation of different ions (protons, calcium, sodium, potassium) in the cells exposed to dcEF, assessed by ion-specific vital dyes [6].
Here, we have cooperation with the group of M. Levin (Harvard, Boston) with Prof. H.H. Epperlein (in our institute) and with Prof. E. Tanaka (CRTD).
For appication of DC-EF we (together with the group of Prof. Gerlach, TUD) have developed a polymer-gel electrode [7].
- Ozkucur N, Monsees TK, Perike S, Do HQ, Funk RH
Local calcium elevation and cell elongation initiate guided motility in electrically stimulated osteoblast-like cells.
PLoS One. 2009 Jul 3;4(7):e6131. PubMed PMID: 19584927; PubMed Central PMCID: PMC2702840 - Ozkucur N, Richter E, Wetzel C, Funk RH, Monsees TK
Biological relevance of ion energy in performance of human endothelial cells on ion-implanted flexible polyurethane surfaces.
J Biomed Mater Res A. 2009 Jun 25. PubMed PMID: 19557788 - Funk RH, Monsees T, Ozkucur N
Electromagnetic effects - From cell biology to medicine.
Prog Histochem Cytochem. 2009;43(4):177-264. Epub 2008 Sep 18. Review. PubMed PMID: 19167986 - Bierbaum S, Douglas T, Hanke T, Scharnweber D, Tippelt S, Monsees TK, Funk RH, Worch H
Collageneous matrix coatings on titanium implants modified with decorin and chondroitin sulfate: characterization and influence on osteoblastic cells.
J Biomed Mater Res A. 2006 Jun 1;77(3):551-62. PubMed PMID: 16498599 - Ozkucur N, Perike S, Sharma P, Funk RH
Persistent directional cell migration requires ion transport proteins as direction sensors and membrane potential
differences in order to maintain directedness.
BMC Cell Biol. 2011 Jan 22;12:4. PubMed PMID: 21255452; PubMed Central PMCID: PMC3042415 - Ozkucur N, Epperlein HH, Funk RH
Ion imaging during axolotl tail regeneration in vivo.
Dev Dyn. 2010 Jul;239(7):2048-57. PubMed PMID: 20549718 - Aryasomayajula A, Derix J, Perike S, Gerlach G, Funk RH
DC microelectrode array for investigating the intracellular ion changes.
Biosens Bioelectron. 2010 Dec 15;26(4):1268-72. Epub 2010 Jul 6. PubMed PMID: 20656468 - Ozkucur N, Song B, Bola S, Zhang L, Reid B, Fu G, Funk RH, Zhao M
NHE3 phosphorylation via PKCη marks the polarity and orientation of directionally migrating cells.
Cell Mol Life Sci. 2014 Dec;71(23):4653-63. doi: 10.1007/s00018-014-1632-1. Epub 2014 May 1. PubMed PMID: 24788043 - Perike S, Özkucur N, Sharma P, Staroske W, Bläsche R, Barth K, Funk RH
Phospho-NHE3 forms membrane patches and interacts with beta-actin to sense and maintain constant direction during cell migration.
Exp Cell Res. 2014 May 15;324(1):13-29. doi: 10.1016/j.yexcr.2014.03.005. Epub 2014 Mar 19. Erratum in: Exp Cell Res. 204 Aug 1;326(1):185. PubMed PMID: 24657527 - Wittig D, Wang X, Walter C, Gerdes HH, Funk RH, Roehlecke C
Multi-level communication of human retinal pigment epithelial cells via tunneling nanotubes
PLoS One. 2012;7(3):e33195. doi: 10.1371/journal.pone.0033195. Epub 2012 Mar 22. PubMed PMID: 22457742; PubMed Central PMCID: PMC3310865