Controlling cell polarization, directional migration and wound healing by high precision pH manipulation

Prof. Matias Simons (ZBSA and Renal Division, University Medical Center Freiburg)

Cellular pH is subject to tight spatial and temporal control by a number of proton transport systems. Local pH regulation can give rise to pH differences between cellular compartments and, even, within one compartment. pH-sensitive processes carried out by pH-sensitive kinases, proteases and cytoskeletal components can trigger spatially and temporally coordinated signaling events, and we are particularly interested in their contribution to cellular polarization.

Our previous results suggest that EGF signaling controls cell polarization of human keratinocytes via the activation of the sodium-proton exchanger NHE1. NHE1-inhibited cells lack proper rear contractions and fail to polarize towards the cathode in low-voltage electric fields. Here, we will use a candidate gene approach to identify pH-sensitive factors in the polarization process. In addition, we want to be able to steer cell polarization and directional migration via the optogenetic control of pH transport.