Online monitoring of metabolism and morphology of peptide-treated neuroblastoma cancer cells and keratinocytes

• Published in: Journal of bioenergetics and biomembranes Vol. 43; no. 3; pp. 275 - 285
• Main Authors: Drechsler, Sabine, Andrä, Jörg
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-06-2011; Springer Nature B.V
• Subjects: Acidification; Animal Anatomy; Animal Biochemistry; Antimicrobial agents; Antimicrobial peptides; Biochemistry; Bioorganic Chemistry; Biosensors; Cancer; Cell death; Cell Line; Cell Line, Tumor; Cell surface; Cellular biology; Chemistry; Chemistry and Materials Science; Cytology; Energy metabolism; Glycolysis; Histology; Humans; Hydrophobic and Hydrophilic Interactions; Impedance; Internet; Keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - metabolism; Melitten - pharmacology; Metabolism; Mode of action; Morphology; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - metabolism; Neuroblastoma - pathology; Organic Chemistry; Oxygen consumption; Peptides; Peptides - chemical synthesis; Peptides - pharmacology; Perfusion; Respiration; Stress; Membrane permeabilization; Biosensor; Glycolysis; Keratinocytes; Neuroblastoma; Impedance; Respiration; HaCaT; Antimicrobial peptide; Cancer
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-011-9350-y

Antimicrobial peptides are promising anti-cancer agents with a unique mode of action. We established the usage of a chip-based sensor to monitor the dynamic interplay between cells on the chip and peptides and compared it with endpoint tests. Human neuroblastoma cancer cells and spontaneously immortalized non-cancer keratinocytes were perfused with representative peptides (NK-2, NK11, and melittin). The sensor system enabled continuous recording of cell layer impedance (adhesion/confluence), oxygen consumption (respiration) and extracellular acidification (glycolysis) and provided insights in cell damage, stress response and recovery. Cells responded differentially to peptide treatment. During perfusion, peptides accumulated on the cell surface until they reached a critical concentration. Preceding to cell death, melittin triggered glycolysis, suggesting stress response. NK-2 induced no change in energy metabolism, but led to an increase in impedance, i.e. a temporarily altered morphology, which appeared to be an excellent parameter to detect subtle structural changes of cell layers.