Membrane Physiology and Biophysics—What Remains to Be Done?

Biological membranes consist of lipid bilayer matrices enriched with integral membrane proteins and membrane-associated proteins. They not only define cells and cell organelles but also represent the main contact area for intercellular communication, for which membrane transport and signaling are indispensable. Because of their high physiological importance and unique physical and chemical properties, biological membranes have been intensively studied for over 100 years, and membrane physiology remains a flourishing and lively research field. Recent years have witnessed great progress in our understanding of the biophysical basis of membrane transport and its role in generating biological electricity and controlling the intracellular milieu. The workings of ion channels and transporters are understood in a degree of detail that was unimaginable when many of us started our scientific careers. Protein sequences and three-dimensional structures are now available for almost every major ion channel and transporter family (Navratna and Gouaux, 2019). Heterologous expression systems and patch clamp electrophysiology can provide functional data of unprecedented accuracy (Neher, 1992; Sakmann, 1992). The identification of amino acid sequences that direct ion channels and transporters to specific intracellular membrane compartments has enabled ion transport proteins that normally reside in intracellular membranes (such as synaptic vesicles or lysosomes) to be expressed and studied on the plasma membrane of mammalian cells (Leisle et al., 2011; Guzman et al., 2015; Eriksen et al., 2016). Moreover, advances in live-cell imaging enable the real-time visualization of intracellular trafficking of ion channels and transporters from protein translation in the endoplasmic reticulum to their arrival at the plasma membrane or site of action (Xiao and Shaw, 2015; Conrad et al., 2018)