Mechanisms of ion-channel-induced membrane permeabilization
Biological membranes protect the cell from toxic agents, allow the uptake of necessary nutrients and the efflux of waste products. A precise control of membrane permeability is essential for life and therefore is a central issue in Biophysics. Despite intensive investigations on the matter, the molecular mechanisms regulating membrane permeabilization are still poorly understood. The present project focuses on the membrane permeabilization induced by a variety of channel-forming proteins. These channels allow the controlled transport of ions and small compounds across membranes, affecting the concentration gradients necessary for cell life and enabling electrical signaling, transmitting specific information throughout any living organism. In the present project, we explore the correlation between the structure and the function of ion channels in both directions. Firstly, we study proteins with known detailed structural information, such as OmpF from E. Coli and VDAC from mitochondria, which serve as a model system for the testing and development of physical models of different complexity. On the other hand, we also explore some proteins of special biomedical interest called viroporins (channels from clinically relevant animal virus) that need better characterization. The strength of the project lies in its interdisciplinary approach. First, we perform electrophysiological recordings at the single molecule level combined with other experimental approaches to show that mesoscopic permeability can be understood in terms of an ensemble of molecular units operating together. We dip into the recorded traces by performing kinetic studies of the channel open probability together with thermodynamic analysis revealing the energy landscape of each process. We also probe the nature of current fluctuations through the exploration of the power spectral density (PSD) of membrane pores and its dependence with frequency. Finally, we use both continuum electrostatics and atomic simulations to rationalize the experimental findings on the grounds of the available structural information.