REGULATION OF EUKARYOTIC CELL PHYSIOLOGY USING ORGANIC BIOELECTRONICS

The field of organic bioelectronics deals with the implementation of conducting polymer science in biology and medicine. The purpose of this thesis was to develop organic bioelectronic devices for the regulation of eukaryotic cell physiology. The specific physiological concepts that the devices aimed to address were activation of voltage-gated ion channels, cellular mechanotransduction and cell adhesion. The conductive polymers that were used in these devices were polypyrrole and poly(3,4ethylenedioxythiophene). These polymers are biocompatible which makes them suitable for studying cell physiology. Five devices are presented in the thesis. These are: a nano-fiber scaffold coated with a conducting polymer for electric cell stimulation with high charge transfer capacity, a microfabricated chip comprising microactuators for mechanical stimulation on a cellular level, a conducting polymer surface and a planar electrochemical transistor for control of cell adhesion, and finally a conducting polymer surface with self-disintegrating properties for non-invasive cell release. To evaluate the ability of these devices to address the key physiological concepts they were designed for. A number of cell lines with individual characteristics were chosen. Electric stimulation via conducting polymer coated nano-fibers was tested with a neuroblastoma cell line expressing voltage-operated Ca channels. A renal epithelial cell line was used to investigate the microactuator chip for mechanical cell stimulation. Renal epithelial cells were also used when investigating devices designed to regulate cell adhesion by interacting with extracellular serum proteins. A human bladder carcinoma cell line was used to examine the self-disintegrating polymer surface for non-invasive cell detachment of adherent cells. The results of the thesis show that it is possible to activate voltage-gated ion channels, induce stimuli that trigger cellular mechanotransduction, and control cell adhesion using organic bioelectronics. LIST OF PUBLICATIONS The thesis is based on the following papers: (Additional work is listed on page 28) I. Nano-fiber scaffold electrodes based on PEDOT for cell stimulation. Maria H. Bolin*, Karl Svennersten*, Xiangjun Wang, Ioannis S. Chronakis, Agneta Richter-Dahlfors, Edwin W.H. Jager and Magnus Berggren. Sensors and Actuators B: Chemical, 2009, 142, 451-456. *contributed equally. II. Mechanical stimulation of epithelial cells using polypyrrole microactuators. Karl Svennersten, Magnus Berggren, Agneta Richter-Dahlfors, Edwin WH Jager. Submitted manuscript. III. Electrochemical modulation of epithelia formation using conducting polymers. Karl Svennersten*, Maria H Bolin*, Edwin W Jager, Magnus Berggren, Agneta Richter-Dahlfors. Biomaterials, 2009, 30, 6257-6264. *contributed equally. IV. Active Control of Epithelial Cell-Density Gradients Grown Along the Channel of an Organic Electrochemical Transistor. Maria H. Bolin*, Karl Svennersten*, David Nilsson, Anurak Sawatdee, Edwin W. H. Jager, Agneta Richter-Dahlfors, and Magnus Berggren. Advanced Materials, 2009, 21, 4379-4382. *contributed equally. V. Electronic control of cell detachment using a self-doped conducting polymer. Kristin M Persson, Roger Karlsson, Karl Svennersten, Edwin W H Jager, Agneta Richter-Dahlfors, Peter Konradsson, Magnus Berggren. Submitted manuscript.