Marisa Eisenberg and colleagues started to develop the model after a PhD student had shown that knocking down myoferlin in cancer cells reduces their invasive behavior. The model was based on the same experimental set-up (upper figure). In this set-up, cancer cells can move from an upper chamber through a matrix and a membrane/microelectrode array to a lower chamber. The lower chamber has a chemoattractant. The change in impedance of the microelectrode array is used as a measure for cell invasiveness.

The scientists introduced seven variables for their model (lower figure). They simulated results after knocking down myoferlin, which confirmed the experimental results. Furthermore the simulation suggests that a significant part of this effect is mediated by matrix metalloproteinases. The results of a PCR-screen are in line with this result.

Upper figure: Real-time impedance-based cell tracking setup via xCELLigence wells. The upper  and lower chambers are separated by a semipermeable membrane and microelectrode array.  Matrigel/ECM sits on top of the microelectrode array, and cells migrate and invade through the upper chamber towards chemoattractant in the lower chamber.

Lower figure: Model for receptor recycling and cell migration and invasion, with processes marked in red affected by myoferlin. Cells proliferate, migrate, and invade following these processes, with cell movement dependent on the growth factor gradient (chemotaxis) and the extracellular matrix gradient (haptotaxis).

Images and captions were kindly provided by Marisa Eisenberg, Mathematical Biosciences Institute, The Ohio State University

Eisenberg, M. C., Y. Kim, R. Li, W. E. Ackerman, D. A. Kniss and A. Friedman "Mechanistic modeling of the effects of myoferlin on tumor cell invasion." Proceedings of the National Academy of Sciences