TY - JOUR
T1 - Elucidating the Signal Responses of Multi-Parametric Surface Plasmon Resonance Living Cell Sensing
T2 - A Comparison between Optical Modeling and Drug-MDCKII Cell Interaction Measurements
AU - Viitala, Tapani
AU - Granqvist, Niko
AU - Hallila, Susanna
AU - Raviña, Manuela
AU - Yliperttula, Marjo
PY - 2013/8/27
Y1 - 2013/8/27
N2 - In vitro cell-based assays are widely used during the drug discovery and development process to test the biological activity of new drugs. Most of the commonly used cell-based assays, however, lack the ability to measure in real-time or under dynamic conditions (e.g. constant flow). In this study a multi-parameter surface plasmon resonance approach in combination with living cell sensing has been utilized for monitoring drug-cell interactions in real-time, under constant flow and without labels. The multi-parameter surface plasmon resonance approach, i.e. surface plasmon resonance angle versus intensity plots, provided fully specific signal patterns for various cell behaviors when stimulating cells with drugs that use para- and transcellular absorption routes. Simulated full surface plasmon resonance angular spectra of cell monolayers were compared with actual surface plasmon resonance measurements performed with MDCKII cell monolayers in order to better understand the origin of the surface plasmon resonance signal responses during drug stimulation of cells. The comparison of the simulated and measured surface plasmon resonance responses allowed to better understand and provide plausible explanations for the type of cellular changes, e.g. morphological or mass redistribution in cells, that were induced in the MDCKII cell monolayers during drug stimulation, and consequently to differentiate between the type and modes of drug actions. The multi-parameter surface plasmon resonance approach presented in this study lays the foundation for developing new types of cell-based tools for life science research, which should contribute to an improved mechanistic understanding of the type and contribution of different drug transport routes on drug absorption.
AB - In vitro cell-based assays are widely used during the drug discovery and development process to test the biological activity of new drugs. Most of the commonly used cell-based assays, however, lack the ability to measure in real-time or under dynamic conditions (e.g. constant flow). In this study a multi-parameter surface plasmon resonance approach in combination with living cell sensing has been utilized for monitoring drug-cell interactions in real-time, under constant flow and without labels. The multi-parameter surface plasmon resonance approach, i.e. surface plasmon resonance angle versus intensity plots, provided fully specific signal patterns for various cell behaviors when stimulating cells with drugs that use para- and transcellular absorption routes. Simulated full surface plasmon resonance angular spectra of cell monolayers were compared with actual surface plasmon resonance measurements performed with MDCKII cell monolayers in order to better understand the origin of the surface plasmon resonance signal responses during drug stimulation of cells. The comparison of the simulated and measured surface plasmon resonance responses allowed to better understand and provide plausible explanations for the type of cellular changes, e.g. morphological or mass redistribution in cells, that were induced in the MDCKII cell monolayers during drug stimulation, and consequently to differentiate between the type and modes of drug actions. The multi-parameter surface plasmon resonance approach presented in this study lays the foundation for developing new types of cell-based tools for life science research, which should contribute to an improved mechanistic understanding of the type and contribution of different drug transport routes on drug absorption.
UR - http://www.scopus.com/inward/record.url?scp=84883154044&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0072192
DO - 10.1371/journal.pone.0072192
M3 - Article
C2 - 24015218
AN - SCOPUS:84883154044
SN - 1932-6203
VL - 8
JO - PLOS ONE
JF - PLOS ONE
IS - 8
M1 - e72192
ER -