title: Dynamic changes of acoustic load and complex impedance as reporters for the cytotoxicity of small molecule inhibitors.
abstract: Cellular motility is the major driving force of numerous biological phenomena including wound healing, immune response, embryogenesis, cancer formation, and metastasis. We studied the response of epithelial FaDu monolayers cultured on gold electrodes of an acoustic resonator (quartz crystal microbalance, QCM) and impedance sensor (electric cell-substrate impedance sensing, ECIS) to externally applied chemical stimuli interfering with cytoskeleton organization. Epithelial cell motility of confluent monolayers is characterized by subtle cell shape changes and variations in the cell-substrate as well as cell-cell distance without net directionality of individual cells. The impact of small molecules such as cytochalasin D, phalloidin, and blebbistatin as well as paclitaxel, nocodazol, and colchicin on actin and microtubules organization was quantified by conventional sensors' readouts and by comparing the noise pattern of the signals which is attributed to cellular dynamics. The responsiveness of noninvasive and label-free techniques relying on cellular dynamics is compared to classical viability assays and changes of the overall impedance of ultrasmall electrodes or acoustic loads of a thickness shear mode resonator. Depending on the agent used, a distinct sensor response was found, which can be used as a fingerprint of the cellular response. Cytoskeletal rearrangements and nuclear integrity were corroborated by fluorescence microscopy and correlated to the readouts of QCM and ECIS.
authors.affiliation: Max Planck Institute for Dynamics and Self-Organization, Laboratory for Fluid Dynamics, Pattern Formation and Nanobiocomplexity (LFPN), Fassberg 17, D-37077 Goettingen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Tarantola
authors.forename: Eva
authors.initials: E
authors.lastname: Sunnick
authors.forename: David
authors.initials: D
authors.lastname: Schneider
authors.forename: Anna-Kristina
authors.initials: AK
authors.lastname: Marel
authors.forename: Angelika
authors.initials: A
authors.lastname: Kunze
authors.forename: Andreas
authors.initials: A
authors.lastname: Janshoff
mesh_terms: D000199:Actins / Q000378:metabolism; D015374:Biosensing Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015638:Cytochalasin D / Q000633:toxicity; D003599:Cytoskeleton / Q000187:drug effects*; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000633:toxicity; D006801:Humans; D017239:Paclitaxel / Q000633:toxicity; D010590:Phalloidine / Q000633:toxicity; D058525:Quartz Crystal Microbalance Techniques / Q000379:methods; D050257:Tubulin Modulators / Q000633:toxicity*
chemical_list: D000199:Actins; D006576:Heterocyclic Compounds, 4 or More Rings; D050257:Tubulin Modulators; D010590:Phalloidine; C472645:blebbistatin; D015638:Cytochalasin D; D017239:Paclitaxel