title: Real-time QCM-D monitoring of cancer cell death early events in a dynamic context.
abstract: Since a few years, the acoustic sensing of whole cell is the focus of increasing interest for monitoring the cytoskeletal cellular response to morphological modulators. We aimed at illustrating the potentialities of the quartz crystal microbalance with dissipation (QCM-D) technique for the real-time detection of the earliest morphological changes that occur at the cell-substrate interface during programmed cell death. Human breast cancer cells (MCF-7) grown on serum protein-coated gold sensors were placed in dynamic conditions under a continuous medium flow. The mass and viscoelasticity changes of the cells were tracked by monitoring the frequency and dissipation shifts during the first 4h of cell exposure to staurosporine, a well-known apoptosis inducer. We have identified a QCM-D signature characteristic of morphological modifications and cell detachment from the sensing surface that are related to the pro-apoptotic treatment. In particular, for low staurosporine doses below 1 µM, we showed that recording the dissipation shift allows to detect an early cell response which is undetectable after the same duration by the classical analytical techniques in cell biology. Furthermore, this sensing method allows quantifying the efficiency of the drug effect in less than 4h without requiring labeling and without interfering in the system, thus preventing any loss of information. In the actual context of targeted cancer therapy development, we believe that these results bring new insights in favor of the use of the non invasive QCM-D technique for quickly probing the cancer cell sensitivity to death inducer drugs.
authors.affiliation: FRE CNRS 3580, Génie Enzymatique et Cellulaire, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France; UMR CNRS 7338, BioMécanique et BioIngénierie, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Nowacki
authors.affiliation: UMR CNRS 7338, BioMécanique et BioIngénierie, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Follet
authors.affiliation: UMR CNRS 7338, BioMécanique et BioIngénierie, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Vayssade
authors.affiliation: UMR CNRS 7338, BioMécanique et BioIngénierie, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Vigneron
authors.affiliation: UMR CNRS 7338, BioMécanique et BioIngénierie, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Rotellini
authors.affiliation: UMR CNRS 7338, BioMécanique et BioIngénierie, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Cambay
authors.affiliation: UMR CNRS 7338, BioMécanique et BioIngénierie, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France; Department of Oral and Maxillofacial Pathology, Tufts University, School of Dental Medicine, 1 Kneeland St, Boston, MA 02111, United States. Electronic address: christophe.egles@utc.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Egles
authors.affiliation: FRE CNRS 3580, Génie Enzymatique et Cellulaire, Université de Technologie de Compiègne, Centre de Recherches de Royallieu, CS 60319, 60203 Compiègne, France. Electronic address: claire.rossi@utc.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Rossi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D015374:Biosensing Techniques / Q000295:instrumentation*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D003199:Computer Systems; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D061986:MCF-7 Cells; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation*; D019311:Staurosporine / Q000008:administration & dosage*; D014159:Transducers
chemical_list: D000970:Antineoplastic Agents; D019311:Staurosporine
keywords: Apoptosis; Human breast cancer cell line MCF-7; Morphology dynamic measurement; Quartz crystal microbalance with dissipation; Staurosporine; Whole cell biosensor