Biomedical subjects

Ralf Kemkemer

Publications and source records attributed to Ralf Kemkemer.

3 recordsLinked to original sources

PubMed2006

Cell orientation by a microgrooved substrate can be predicted by automatic control theory.

Cells have the ability to measure and respond to extracellular signals like chemical molecules and topographical surface features by changing their orientation. Here, we examined the orientation of cultured human melanocytes exposed to grooved topographies. To predict the cells' orientation response, we describe the cell behavior with an automatic controller model. The predicted dependence of the cell response to height and spatial frequency of the grooves is obtained by considering the symmetry of the system (cell + substrate). One basic result is that the automatic controller responds to the square of the product of groove height and spatial frequency or to the aspect ratio for symmetric grooves. This theoretical prediction was verified by the experiments, in which melanocytes were exposed to microfabricated poly(dimethylsiloxane) substrates having parallel rectangular grooves of heights (h) between 25 and 200 nm and spatial frequencies (L) between 100 and 500 mm(-1). In addition, the model of the cellular automatic controller is extended to include the case of different guiding signals acting simultaneously.

Biocompatible Materials↗

PubMed2004

Cell shape normalization, dendrite orientation, and melanin production of normal and genetically altered (haploinsufficient NF1)-melanocytes by microstructured substrate interactions.

Little is known about how functional regulation failure in genetically altered cells is influenced by topographical confinement of cells, a situation often present in tissues in vivo. We used cultured melanocytes derived from human skin samples as a model system for such investigations. Normal melanocytes have a very well defined shape consisting of a cell body and two dendrites arranged 180 degrees relative to each other. In contrast, neurofibromin 1-melanocytes (NF1-melanocytes) have up to a 50% reduction of neurofibromin 1, which results in an altered morphology that can be easily measured. NF1-melanocytes deviate from the defined structure of normal melanocytes by forming more than two dendrites per cell. We show that morphology consequences of genetically altered melanocytes can be canceled if cells interact with substrates microstructured by stripes that apply mechanophysical signals in the form of physical topography. The strength of the mechanophysical signal was varied systematically by increasing the height of the microstructures. Melanocytes respond to surface topographical features that are larger than 50 nm and have lateral confinements smaller 4 microns. The response of normal and NF1-melanocytes to different topographies was analyzed quantitatively by determining density distributions for the number of dendrites per cell, the angles between dendrites, and the orientation imprinted in the substrate. The synthesis of melanin, a pigment produced by melanocytes, differs in the case of genetically altered NF1- and normal melanocytes. In both cases, the interaction with microstripes enhanced melanin production significantly. This enhanced melanin production is speculated to be caused by the mechanical stabilization of the dendrites by substrate guidance.

Cell Size↗

PubMed2002

Increased noise as an effect of haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1 in vitro.

In human diseases related to tumor-suppressor genes, it is suggested that only the complete loss of the protein results in specific symptoms such as tumor formation, whereas simple reduction of protein quantity to 50%, called haploinsufficiency, essentially does not affect cellular behavior. Using a model of gene expression, it was presumed that haploinsufficiency is related to an increased noise in gene expression also in vivo [Cook, D. L., Gerber, A. N. & Tapscott, S. J. (1998) Proc. Natl. Acad. Sci. USA 95, 15641-15646]. Here, we demonstrate that haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1 (NF1) results in an increased variation of dendrite formation in cultured NF1 melanocytes. These morphological differences between NF1 and control melanocytes can be described by a mathematical model in which the cell is considered to be a self-organized automaton. The model describes the adjustment of the cells to a set point and includes a noise term that allows for stochastic processes. It describes the experimental data of control and NF1 melanocytes. In the cells haploinsufficient for NF1 we found an altered signal-to-noise ratio detectable as increased variation in dendrite formation in two of three investigated morphological parameters. We also suggest that in vivo NF1 haploinsufficiency results in an increased noise in cellular regulation and that this effect of haploinsufficiency may be found also in other tumor suppressors.

Case-Control Studies↗