Intracellular Molecular Processes Affected by pH

Many molecules, including important molecular components of living cells, possess functional groups capable to release or abstract a proton, which is a process strongly dependent on pH. These proton transfer phenomena lead to changes in the electric charge distribution within a biopolymer molecule. As the electrostatic interactions are of a long-range nature, these processes must have a significant contribution to both the inter-and intramolecular interactions and hence to the rates of molecular associations, and stability of biopolymers and bio-molecular complexes. Moreover, protons are promoters and mediators in chemical reactions occurring in solutions, which results in the pH dependence of enzyme catalysis. Therefore the pH is an important physiologic variable controlling biomolecular structure, dynamics, and function. Here, our main interest is in processes occurring inside living cells.

Observations that many biomolecular processes, occurring in vitro and in vivo are pH-dependent, and the ability to measure and control pH in nano-sized environments, including living cells, led, in the present time, to a wide-spread interest in biomolecular processes affected by pH and/or triggered by pH jumps. The best known and the most impressive example of an intracellular process triggered by a pH-jump is provided by the simultaneous opening of the endosome and viral envelope caused by acidification of the endosome during influenza virus infection. There are many more interesting phenomena and problems in this area. In the present Research Topis, we would like to review these intracellular processes, with particular focus on recent developments in the theory and experiment.

This Research Topic is interested in review and research articles that focus on, but is not limited to, the following themes:

•  Understanding pH in confined nano-sized spaces like living cells and their organelles.

•  The physical basis for pH-sensitivity of bio-molecular structure, dynamics, and function.

•  Experimental and computational methods for the analysis of protonation equilibria in complex bio-molecular systems.

•  Experimental methods for determining pH in biologically relevant systems including pH imaging in cells. 

•  Endosomal entry and its acidification and viral infection. 

•  The pH control of cell homeostasis, metabolism, division, and apoptosis. 

•  Intracellular pH in cancer and Alzheimer’s disease