Life as we know it would not be possible without the proper compartmentalization of biological systems. Compartmentalization insures that physiochemical reactions and biological processes remain within a confined area of a cell or of a multi-cellular organism and that these processes do not interfere with each other. This, in turn, allows for highly specialized functions to develop. For the whole to function properly, specialized compartments must communicate efficiently through a highly complex molecular transport system.
At the microscopic level, molecular transport primarily concerns the movement of ions, small molecules and macromolecules across lipid bilayers, which constitute the membranes of cells and subcellular organelles. Such cross-membrane transport is the initial step of many biological processes such as cellular respiration. At the macroscopic level, tightly controlled molecular transport across physiological barriers, such as epithelia within and among tissues and organs, is essential to the constant regulation of local and global homeostatic environments. These are of central importance for living organisms to function. As such, it is tightly regulated molecular transport and optimum local environments that enable specialized cells, organs, and the body as a whole to obtain what they need for optimum performance.
Over millions of years of evolution, biological systems have developed various transport processes to move molecules across lipid bilayer membranes. The primary mechanisms are passive diffusion, channel mediated, transporter mediated and vesicle mediated transport, as summarized below.
Table: The major processes of cross-membrane transport of biological and therapeutic agents
Research advances during the last few decades have shed light on the critical importance of transporter proteins in regulating the movement and homeostasis of various bioactive molecules inside the body. Historically, the movement of most small molecules was believed to be driven primarily by passive diffusion; it is now generally agreed that cross-membrane transport of most small molecules, including endogenous agents and xenobiotics, is tightly regulated by approximately 1000 transporter proteins.
Improved understanding of such complex and highly regulated transport processes through systematic studies on transporter protein offers tremendous opportunities for basic biomedical research and pharmaceutical development. This is exemplified by the recent regulatory requirements on transporter testing for Drug-Drug Interaction (DDI) assessment, and by the success of many transporter-targeting drugs such as dapagliflozin, sertraline and tiagabine.