Engineering channels: Atomic biology
- Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612
Ion channels are protein valves that control an enormous range of biological function. Atomic-scale properties of channel proteins control macroscopic flows across otherwise insulating membranes of cells and subcellular compartments, and so the study of channels is a study in atomic biology. Ion channels are intrinsically multiscale devices that allow the amino acid side chains of a protein to control nerve signaling and coordinate muscle contraction—including the contraction that allows the heart to pump blood—and a host of other biological activities. A Google search for “ion channels” or “channelopathy” (1) shows the enormous importance of channels in biology and medicine.
Atomic Biology
Ion channels are natural nanodevices that use atomic structures to control macroscopic flows. Ion channels depend on evolutionary engineering on the atomic scale. Picostructures—side chains only tens of picometers in dimension—control the specific chemical properties of ion channels by crowding ions and side chains in a tiny space (2). Simulations show that crowding of ions can explain the properties of different types of channels when using models that contain only two parameters (3). These parameters are not adjusted as solutions are changed or as the channel is mutated from one type to another. Some mutations produce different valves that specifically control the fluxes of different types of ions.
Nature has also shown how to build picovalves that can be turned on and off by a wide range of stimuli, whether chemical, physical, or biological. Nature has built many channel types that respond selectively (in milliseconds) to one or two molecules of an agonist or drug (4). Sakmann and Neher (5) along with others (6) have shown us how to record single channels, and single-channel recording can be done in thousands of laboratories today.
Biotechnology tries to take advantage of this knowledge and experience with biological channels to build systems that …
*E-mail: beisenbe{at}rush.edu
