Polymer-protein association

If peptide residues are converted to peptoid residues, the conformational heterogeneity of the polymer backbone is likely to increase due to cis/trans isomerization at amide bonds. This will lead to an enhanced loss of conformational entropy upon peptoid/protein association, which could adversely affect binding thermodynamics. A potential solution is the judicious placement of bulky peptoid side chains that constrain backbone dihedral angles. 

When strength-of-materials considerations are not signilicant design features of an anticipated device, one can use strategies that seek to prevent the adsorption of proteins and cells. As Table 6.1 illustrated, a strategy to accomplish this would be to use hydrophilic polymers. The interaction of proteins and surfaces is a complex subject and depends on the nature of the protein, associations with other proteins, time, shear, and other factors including the chemistry of the surface. 

All except tropomyosin form larger molecules. Tubulin, under the influence of GTP, aggregates into microtubules G-actin polymerizes to F-actin myosin forms thick filaments by tail-to-tail interaction and /3-actin polymerizes to microfilaments. /3-Actin is similar but not identical to G-actin. Tropomyosin is a fibrous protein associated with the F-actin polymer. It controls myosin-actin interaction under the influence of troponin. 

This chapter relates to some recent developments concerning the physics of out-of-equilibrium, slowly relaxing systems. In many complex systems such as glasses, polymers, proteins, and so on, temporal evolutions differ from standard laws and are often much slower. Very slowly relaxing systems display aging effects [1]. This means in particular that the time scale of the response to an external perturbation, and/or of the associated correlation function, increases with the age of the system (i.e., the waiting time, which is the time elapsed since the preparation). In such situations, time-invariance properties are lost, and the fluctuation-dissipation theorem (FDT) does not hold. 

There are of course, many facets of polymers for which our under-standing is far from complete. Polymers with associating groups bonded to their chains, polymer crystallization, liquid crystalline polymers and charged polymers are examples of areas of active research in polymer physics. These four particular examples are also very pertinent to understanding the functions of important biopolymers, such as DNA, RNA, proteins, and polysaccharides. By learning the fundamentals of chain conformations, thermodynamics, elasticity, and mobility, the readers of this book should be ready to consider these more challenging facets. 

FIG. 11 Schematic illustration of the different types of complexes (a) with long polymers (interchain aggregates are formed essentially in the case of Coulombic complexation of polyelectrolyte and protein) (b) with short amphiphilic polymers (hydrophobic association). 

N. Kozer, Y. Y. Kuttner, G. Haran, G. Schreiber, Protein-protein association in polymer solutions from dilute to semidilute to concentrated, Biophys. 2007, 92, 2139-2149. 

The complexation behaviour of proteins with dilute solutions of PAA and a random polyampholyte DMAEM-AA-MM A was studied by turbidimetric titration [87]. Polyampholyte-polyampholyte interaction (self-aggregation) and polyampholyte-protein complexation was studied as a function of pH and polymer dosage. Large increases in turbidity were observed for polyampholyte-protein mixtures compared with polyampholyte alone. However, protein analysis of the supernatant and precipitate revealed that only about 10% of the protein precipitates with the random polyampholyte while 90% of the protein remains in the equilibrium liquid. An experiment with PAA and oppositely charged protein shows the opposite trend with 90% precipitation of protein. Hence, great care needs to be taken in the interpretation of turbidimetric titration data. It has been reported that polyampholyte-protein associates behave with lowered immunogenic activity [88]. 

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