Cell-Stretch Device Engineering


Background and Research Focus

Mechanosensitive ion channels (MSC) represent the biophysical interface between physical stimuli such as pressure or tensile forces and cellular and systemic responses up to tactile sensations such as ‘touch’. Dysfunction of MSC can result in severe organ failure, but also in reverse can organ dysfunction lead to altered expression and function of MSCs. For example, in the heart, a link between transient receptor potential channels (TRP) and heart failure has been established with an increased mechanical stress within the heart resulting in an increased expression profile of such channels. Because some TRP channels conduct important ions such as Ca2+, a relationship with disrupted Ca2+ homeostasis in such hearts is probable. We are interested in how passive stretching of individual heart cells that have been adherently coated on polymer membranes interferes with Ca2+ homeostasis in normal and diseased hearts. A major focus here lies in Ca2+ influx through MSCs, the mechanism of this influx and the identification of the underlying channel subclass (e.g. by use of specific blockers). Additionally, we also use our engineering expertise to push the development of biomechanical stretch devices for cyclic and static passive stretching of individual cardiomyocytes beyond the technology of conventional, linear stretch device systems which can only apply stretch to individual cells in one uniaxial direction (see figure B). In particular, we design novel, fully automated isotropic stretch systems that translate radial stretch on to a circular polymer membrane to induce cell wall tensions more closely reflecting those experienced by single cells within the hollow organ of the heart. Cell reactions thus studies can then be compared to linear stretch profiles to obtain a better understanding of cellular responses towards isotropic shear stress. Similar to our device systems for skeletal muscle (‘MyoRobot’), we use mechatronics expertise to drive such systems into fully programmable, automated systems for biomedical cell research.

Critical Illness Myopathie

Figure: Biomedical engineering of ‚Cell Stretch‘ technologies for biomedical research on mechanobiology of cells. A, uniaxial, linear cell stretcher with polymer-membrane onto which atrial cardiac cells have been adherently cultured, labelled with a Ca2+ fluorescence dye and observed under a confocal laser scanning microscope. Stretched cells take up external Ca2+ after readdition of Ca2+ to the bathing medium. B, isotropic cell stretcher design for translation of a radial strain component onto a circular PDMS-membrane to study cell reactions in response to isotropic mechanical stress. C, isotropic (biaxial) stretch behavior of the PDMS membrane validated with fluorescent beads coated onto the membrane.

Our goal is to develop a fully-automated cell stretch system that can be used in near future in biomedical research and biomedical cell technologies to study mechanotransduction and mechanical signaling in different cell types adaptable to all types of microscopes.


Literature

  • Friedrich O, Wagner S, Battle AR, Schürmann S, Martinac B (2012). Mechano-regulation of the beating heart at the cellular level – Mechano-sensitiv channels in normal and diseased heart. Prog Biophys Mol Biol 110: 226-238.
  • Yost MJ, Simpson D, Wrona K, Ridley S, Ploehn HJ, Borg TK, Terracio L (2000). Design and construction of a uniaxial cell stretcher. Am J Physiol Heart Circ Physiol 279: H3124-H3130.

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