Flow of macromolecules

Muller AJ (1989) Extensional flow of macromolecules in solution, Ph D Thesis, University of Bristol, Physics Department... 

To fully understand the behavior of biological materials we need to address the issue of viscoelasticity. When a weight is placed on viscoelastic material, there is an instantaneous elastic response and a time-dependent viscous response (see Figure 7.1). For polymers the elastic response reflects the change in macromoleular conformation, which is usually time independent if no bonds are broken. The viscous response is the flow of macromolecules by each other similar to what happens during the flow of fluids in a tube. Fluid flow is a time-dependent process. Polymers exhibit viscoelastic behavior because they have both a time-independent response and a time-dependent response. 

A key factor determining the performance of ultrafiltration membranes is concentration polarization due to macromolecules retained at the membrane surface. In ultrafiltration, both solvent and macromolecules are carried to the membrane surface by the solution permeating the membrane. Because only the solvent and small solutes permeate the membrane, macromolecular solutes accumulate at the membrane surface. The rate at which the rejected macromolecules can diffuse away from the membrane surface into the bulk solution is relatively low. This means that the concentration of macromolecules at the surface can increase to the point that a gel layer of rejected macromolecules forms on the membrane surface, becoming a secondary barrier to flow through the membrane. In most ultrafiltration appHcations this secondary barrier is the principal resistance to flow through the membrane and dominates the membrane performance. 

Although SynChropak GPC supports have excellent efficiencies for small molecules at various flow rates, macromolecules, because of their low diffusion constants, exhibit band spreading when linear velocities are increased. This effect increases with molecular weight, as seen in Fig. 10.11 (4). It should be noted that proteins are usually homogeneous in size and thus yield better efficiencies than polymers, which are usually heterogeneous. For preliminary analy-... 

Hydrodynamic chromatography (HdC) is a relatively new technique, especially in molecular weight separation. It was first investigated in 1969 by DiMarzio and Guttman (1,2) and was called separation by flow (3,4). Small started calling it hydrodynamic chromatography in 1974 (5). The application of this technique was first concerned with the separation of particle size. Prud homme applied it to the molecular weight separation of macromolecules in 1982 (6). 

On the basis of the above data it has been hypothesized that the conductivity of PFCM is due not to the contact between the filler particles but the current passes across the thin (less than 1 -2 microns) polymer interlayers. The conductivity arises when a spontaneous pressure exceeding the threshold value develops in the material. The overstresses apparently arise as a result of PP crystallization in the very narrow gaps between the filler particles [312], Since crystallization must strongly affect the macromolecular conformation whereas the narrowness of the gap and fixed position of molecules on the filler prevent it, the heat released in the process of crystallization must, in part, be spent to overcome this hindrance, whereby a local high pressure may arise in the gap. This effect is possible only where there are gaps of the size comparable with that of macromolecules. The small gap thickness will also hamper pressure relaxation, since the rate of flow from such a narrow clearance should be negligibly small. 

Many authors studying the formation of ECC from melts and solutions suggested that preliminary unfolding and extension of macromolecules occurs. Keller and Maehin25 have shown that in all known cases (including such extreme variants as the crystallization of natural rubber under extension and a polyethylene melt under flow) the same initial process of linear nucleation occurs and fibrillar structures is formed by the macromolecu-lar chains oriented parallel to the fibrillar axes27. ... 

The osmotic pressure is a property that has proven to be especially valuable in the study of solutions of macromolecules, including those of biologic and polymeric interest. The apparatus for measuring this quantity is shown schematically in Figure 7.10. Two compartments are separated by a membrane that will allow the flow of liquid solvent between the two chambers. If solvent is added, flow will occur until the liquid level on the two sides of the membrane is the same. 

The fraction of macromolecules which have been degraded ( ) is equal to the volume of all the fluid elements which satisfy Eq. (102) divided by the total flow across the orifice. Assuming a constant velocity profile at the orifice, in this case is just equal to (r/r0)2, with r0 being the radius of the orifice. 

There is considerable experimental evidence indicating loss of biological activity of macromolecules such as globular proteins and enzymes at gas-Hquid [57], liquid-solid (Fig. 26) [107] and liquid-liquid [108] interfaces. The extent of inactivation has been shown to be strongly influenced by the prevailing flow field and by, many other factors including the presence and/or absence of additives and contaminants and the type of solid surfaces (Figs. 27 and 28) [107]. 

Field-Flow Fractionation Analysis of Macromolecules and Particles,... 

The velocity, viscosity, density, and channel-height values are all similar to UF, but the diffusivity of large particles (MF) is orders-of-magnitude lower than the diffusivity of macromolecules (UF). It is thus quite surprising to find the fluxes of cross-flow MF processes to be similar to, and often higher than, UF fluxes. Two primary theories for the enhanced diffusion of particles in a shear field, the inertial-lift theory and the shear-induced theory, are explained by Davis [in Ho and Sirkar (eds.), op. cit., pp. 480-505], and Belfort, Davis, and Zydney [/. Membrane. Sci., 96, 1-58 (1994)]. While not clear-cut, shear-induced diffusion is quite large compared to Brownian diffusion except for those cases with very small particles or very low cross-flow velocity. The enhancement of mass transfer in turbulent-flow microfiltration, a major effect, remains completely empirical. 

Capillary electrophoresis offers several useful methods for (i) fast, highly efficient separations of ionic species (ii) fast separations of macromolecules (biopolymers) and (iii) development of small volume separations-based sensors. The very low-solvent flow (l-10nL min-1) CE technique, which is capable of providing exceptional separation efficiencies, places great demands on injection, detection and the other processes involved. The total volume of the capillaries typically used in CE is a few microlitres. CE instrumentation must deliver nL volumes reproducibly every time. The peak width of an analyte obtained from an electropherogram depends not only on the bandwidth of the analyte in the capillary but also on the migration rate of the analyte. 

Eigen s theory describes the self-organisation of biological macromolecules on the basis of kinetic considerations and mathematical formulations, which are in turn based on the thermodynamics of irreversible systems. Evolutionary processes are irreversibly linked to the flow of time. Classical thermodynamics alone cannot describe them but must be extended to include irreversible processes, which take account of the arrow of time (see Sect. 9.2). Eigen s theory is based on two vital concepts ... 

Basic to molecular biology is the concept that DNA and RNA are macromolecules that convey information. The sequence of purine and pyrimidine bases in DNA encodes all the information needed to form and direct the chemical reactions within cells. This information thus encodes all catalytic, regulatory, and structural proteins contained within an organism. The flow of information from DNA to RNA to proteins is... 

Figure 9.30 Flow diagram of the energy chain from food to essential processes in human life. The ATP utilised by the NayK ATPase maintains the ion distribution in nerves that is essential for electrical activity and, in addition, maintains neurotransmitter synthesis, both of which provide communication in the brain and hence consciousness, learning and behaviour (Chapter 14). ATP utilisation by myosin ATPase is essential for movement and physical activity. ATP utilisation by the flagellum of sperm is essential for reproduction and ATP utilisation for synthesis of macromolecules is essential for growth.

The blood first reaches the glomerulus, the filter unit of the nephron. The glomerular filtrate, i.e. blood deprived of macromolecules and blood cells, passes through the tubular lumen. The blood which is not filtered, flows through the efferent arteriole into the network of capillaries around the tubules suppl5dng the proximal and distal tubules with blood. 

The transport mechanisms that operate in distribution and elimination processes of drugs, drug-carrier conjugates and pro-drugs include convective transport (for example, by blood flow), passive diffusion, facilitated diffusion and active transport by carrier proteins, and, in the case of macromolecules, endocytosis. The kinetics of the particular transport processes depend on the mechanism involved. For example, convective transport is governed by fluid flow and passive diffusion is governed by the concentration gradient, whereas facilitated diffusion, active transport and endocytosis obey saturable MichaeUs-Menten kinetics. 

Model simulating the hydrodynamic properties of a chain macromolecule consisting of a sequence of beads, each of which offers hydrodynamic resistance to the flow of the surrounding medium and is connected to the next bead by a rigid rod which does not. The mutual orientation of the rods is random. 

---