The ability of cells to move and orient within concentration gradients of chemical attractants or repellents is of central importance for many physiological and pathophysiological conditions encountered among others during development, wound healing, or tumor growth.

We recently found that cell migration of single transformed MDCK-F cells in the absence of such external chemical gradients is characterized by a variety of anomalous properties. A superdiffusive increase of the mean squared displacement of the cell ensemble, non-Gaussian spatial probability distributions, and power-law decays of the velocity autocorrelations are the basic observations. The application of a fractional mathematical model revealed that long-term memory processes are the origin of this behavior.

We now quantified the influence of an external gradient of the chemokine fibroblast growth factor 2 (FGF-2) on the dynamics of MDCK-F cell migration. We were particularly interested in the contribution of TRPC1 channels to the chemotactic response since these channels were shown to be involved in nerve growth cone path finding. Cell migration was monitored by means of time lapse videomicroscopy, and a stable concentration gradient of FGF-2 was created with IBIDI chemotaxis chambers. TRPC1 channel activity was modified genetically (overexpression / siRNA) or pharmacologically. For comparison we also blocked components of the FGF-2 signaling cascade.

MDCK-F cells are moving with a typical velocity of ~0.9 mm/min without external stimuli, whereas chemical gradients can induce additional directed velocities. This influence was quantified by extending the mean squared displacement of the fractional model with an additional drift velocity term v_drift² t². Overexpression of the TRPC1 channels leads to an enhanced mean drift velocity of v_drift = 0.26 mm/min in the direction of the chemical gradient. By contrast, silencing of the TRPC1 channel reduces the response to v_drift = 0.14 mm/min. A similar reduction is obtained with GsMTx-4, an inhibitor of mechanosensitive channels. Blocking the FGF-2 signaling cascade with the phospholipase C inhibitor U73122 reduces the mean drift velocity v_drift to 0.15 mm/min and 0.07 mm/min for cells with TRPC1 overexpression and TRPC1 siRNA, respectively. The phosphor-inositide 3-kinase inhibitor Wortmannin completely blocked chemotaxis (v_drift = 0) while it had almost no effect on the velocity of undirected migration.

It is noteworthy, that the characteristic anomalous features of cell dynamics are present in chemotacting cells, too. Thus, the extension of the fractional model framework can also be applied to cells moving in external chemical gradients.