Session B7: Bionanotechnology: Application and Fundamental Aspects of Processes at Nano-scale

Ion Channels as Nanodevices

Ion channels are proteins surrounding a hole that allow substances to cross biological membranes. The concentration or current of these substances controls an enormous range of biological function: ion channels are nearly as important in biology as transistors in computers. Ion channels have a stable structure (on biological time scales $>$ 0.1$\mu $sec) once open and so current through them can be analyzed by `physics as usual'. The permanent charge on the wall of the channel is large and the volume is tiny, so the number density of ions in the channel is very large, $>$10 M. Physical properties of channels can be understood from the balance between electrical and van der Waals forces of charge crowded into a tiny space. Many biological properties of channels can be understood in the engineering tradition of devices: channels follow reasonably robust `device equations' determined by their specific structural design and general physical environment. Channel research seeks to understand these device equations in \textbf{\textit{just}} enough detail to control them. Channels---like most engineering devices---function away from equilibrium, so spatially non-uniform boundary conditions and non-equilibrium statistical mechanics must be used in their description. Atomic scale simulations pose certain problems since trace concentrations of ions ($<\mu {\rm M})$ often control biological function and ions flow on time scales very much slower than the time steps of simulations. Atomic scale simulations of micro${\rm M}$ activities requires enormous numbers of water molecules ($>$10$^{11})$; direct simulation of ionic current involves many billions ($>$10$^{11})$ of time steps, suggesting that analysis must be multiscale if it is to be useful. This should come as no surprise, since the function of ion channels is inherently multiscale: ion channels act as nanovalves, nanodevices that allow details of atomic structure to control macroscopic flows and biological function.   

Fluctuation driven active molecular transport in passive channel proteins

Living cells interact with their extracellular environment through the cell membrane, which acts as a protective permeability barrier for preserving the internal integrity of the cell. However, cell metabolism requires controlled molecular transport across the cell membrane, a function that is fulfilled by a wide variety of transmembrane proteins, acting as either passive or active transporters. In this talk it is argued that, contrary to the general belief, in active cell membranes passive and spatially asymmetric channel proteins can act as active transporters by consuming energy from nonequilibrium fluctuations fueled by cell metabolism. This assertion is demonstrated in the case of the E. coli aquaglyceroporin GlpF channel protein, whose high resolution crystal structure is manifestly asymmetric. By calculating the glycerol flux through GlpF within the framework of a stochastic model, it is found that, as a result of channel asymmetry, glycerol uptake driven by a concentration gradient is enhanced significantly in the presence of non-equilibrium fluctuations. Furthermore, the enhancement caused by a ratchet-like mechanism is larger for the outward, i.e., from the cytoplasm to the periplasm, flux than for the inward one, suggesting that the same non-equilibrium fluctuations also play an important role in protecting the interior of the cell against poisoning by excess uptake of glycerol. Preliminary data on water and sugar transport through aquaporin and maltoporin channels, respectively, are indicative of the universality of the proposed nonequilibrium-fluctuation-driven active transport mechanism. \\ This work was supported by grants from the Univ. of Missouri Research Board, the Institute for Theoretical Sciences and the Department of Energy (DOE Contract W-7405-ENG-36), and the National Science Foundation (FIBR-0526854).   

Pressure-driven DNA polymer transport in microfluidic and nanofluidic channels

The transport of DNA and proteins within micro- and nanofluidic channels is of central importance to ``lab-on-a-chip'' bioanalysis technology. As fluidic devices shrink, a new regime is encountered where critical device dimensions approach the molecular scale, and the behavior of polymers often departs significantly from the bulk. Here, we present a study of the pressure-driven transport of individual DNA molecules in 175 nm -- 3.8 $\mu $m high silica channels. Two distinct transport regimes were observed: The pressure-driven mobility of DNA increased with molecular length in channels higher than a few times the molecular radius of gyration, whereas DNA mobility was practically independent of molecular length in thin channels. In addition, both the Taylor dispersion and the self-diffusion of DNA molecules were observed to decrease significantly in confined channels, each obeying a power-law scaling relationship. These unusual transport properties are shown to be rooted in the statistical nature of DNA polymer coils. Our results show that simple fluidic channels can be engineered to achieve either hydrodynamic DNA length separation or uniform transport with minimal dispersion using pressure-driven flows.   

The Transportation System Inside a Living Cell

A living cell has an infrastructure much like that of a city. We will describe the transportation system that consists of roads (filaments) and molecular motors (proteins) that haul cargo along these roads. This transportation system is essential for such diverse processes as neuronal function and mitochondrial transport. While there have been studies of how motors function at the single molecule level, and studies of the structure of filamentary networks, studies of how the motors effectively use the networks for transportation have been lacking. We will give an example showing that pigment cells regulate transport by controlling how often pigment granules switch from one filament to another, rather than by altering individual motor activity at the single molecule level, or by relying on structural changes in the network.   

Bio-functionalized Nanotube Membranes For DNA Separation

The studies of translocation and transport of ions, biopolymers, and other genetics materials is very important in medical and scientific communities. The transport of biopolymers such as RNA, DNA, and polypeptides across membrane occurs in many biological systems. Examples include the transport of RNA molecules and transcription factors through nuclear pores, injection of DNA from a virus head into the host cell, and the uptake of oligonucleotides by specific membrane proteins. Another example is the transport of ions through protein ion channels across cell membranes, which converts the concentration of transported analytes through a channel into change in channel conductance. Nature's highly selective biosensor are based on molecular-recognition of one species of interest in the presence of others. In this presentation, I will discuss the fabrication of a new DNA biosensor. I will also talk about the transport behavior of DNA molecules through nanotubes. These sensors based on monodisperse ensemble of gold nanotubes. Single stranded oligonucleotides were immobilized onto the inner walls of nanotubes. These bio/nano-membranes selectively transport complementary DNA across the membrane with selectivity greater than 5 was observed. With these membranes, single nucleotide polymorphism detection is also demonstrated.