Abstract
Protein-based polymers can be designed in which self-assembly occurs as the temperature is raised above the onset temperature, Tt, of an inverse temperature transition for hydrophobic folding and assembly. Instead of changing the temperature, however, by many means the value of Tt can be lowered from above to below an operating temperature to drive hydrophobic folding and assembly. This is the ΔTt- mechanism. Modulation of charges on the polymer provides the most dramatic means of controlling Tt and therefore becomes the most effective means for controlling self-assembly. The formation of charge raises the value of Tt and causes disassembly, whereas neutralization of charge by lowering degree of ionization or by increasing ion-pairing drives self-assembly.
For example, a polymer with one Asp(COO−) or Glu(COO−) per 30 residues can be in solution with its Tt above 100°C. Titration with a cationic drug lowers Tt to below 25°C and results in self-assembly into a drug delivery vehicle capable of a constant release profile for a constant surface area, and the vehicle simply disperses as the drug is released. Similarly an anionic drug can induce self-assemby of a cationic, e.g., Lys(NH3+)-containing, protein-based polymer.
Two solutions of protein-based polymers, one polymer with negative charges, e.g., COO−, and the other with positive charges, e.g., NH3+ and both with hydrophobic residues sufficient to shift the pKa values of their respective functional groups, can exhibit their individual inverse temperature transitions at temperatures much higher than body temperature, even greater than 100°C. On combining the two solutions, the polymers self-assemble with a Tt below room temperature. Each polymer by ion pairing with the other dramatically lowers the temperature of the inverse temperature transition for polymer self-assembly. The effectiveness of this self-assembly of two oppositely charged protein-based polymers increases as the individual hydrophobic-induced pKa shifts are larger and as steric matching occurs in the ion-pairing between the pair of polymers. Furthermore, the same protein-based polymer can contain both positive and negative charges with hydrophobically shifted pKa values to become locked in self-assembled structures. This bears analogy to certain globular proteins, which on unfolding would similarly self-assemble to form the neurofibrillary tangles and amyloid plaques of Alzheimers and related diseases.
In summary, ion-pairing within properly designed protein-based polymers results in self-assembling materials and structures by means of the ΔTt-mechanism.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Urry, D.W., Trapane, T.L., and Prasad K.U. (1985) Phase-Structure Transitions of the Elastin Polypentapeptide-Water System Within the Framework of Composition-Temperature Studies, Biopolymers 24, 2345–2356.
Urry D.W. (1993) Molecular Machines: How Motion and Other Functions of Living Organisms Can Result from Reversible Chemical Changes, Angew. Chem. (German) 105, 859–883, 1993; Angew. Chem. Int. Ed. Engl., 32, 819–841.
Urry, D.W., Gowda, D.C., Parker, T.M., Luan, C.H., Reid, M.C., Harris, C.M., Pattanaik, A., and Harris, R.D. (1992) Hydrophobicity Scale for Proteins Based on Inverse Temperature Transitions, Biopolymers 32, 1243–1250.
Urry, D.W., Peng, S.Q., and Parker, T.M. (1993) Delineation of Electrostatic-and Hydrophobic-Induced pKa Shifts in Polypentapeptides: The Glutamic Acid Residue, J. Am. Chem. Soc. 115, 7509–7510.
Urry, D.W., Peng, S.Q., Parker, T.M., Gowda, D.C., and Harris, R.D. (1993) Relative Significance of Electrostatic-and Hydrophobic-Induced pKa Shifts in a Model Protein: The Aspartic Acid Residue, Angew. Chem. (German) 105, 1523–1525, 1993; Angew. Chem. Int. Ed. Engl. 32, 1440–1442.
Urry, D.W., Peng, S.Q., Gowda, D.C., Parker, T.M., and Harris, R.D. (1994) Comparison of Electrostatic-and Hydrophobic-induced pKa Shifts in Polypentapeptides: The Lysine Residue, Chemical Physics Letters 225, 97–103.
Urry, D.W. (1992) “Free Energy Transduction in Polypeptides and Proteins Based on Inverse Temperature Transitions,” Prog. Biophys. Molec. Biol. 57, 23–57.
The nature of the water of hypdrophobic hydration is considered to be like the hydrogen bonded water forming pentagonal structures surrounding alkane gases as found by Stackelberg and Muller (1951) Nuturwissenscaften 38, 456, and at the surface of hydrophic side chains such as leucine (Leu, L) in the crystal structure of the protein, crambin, by M. Teeter (1984) Proc. Natl. Acad. Sci. 81, 6014–6018.
Urry, D.W., Luan, C.H., Harris, R.D., and Prasad, K.U. (1990) Aqueous Interfacial Driving Forces in the Folding and Assembly of Protein (Elastin)-Based Polymers: Differential Scanning Calorimetry Studies, Polym. Preprints, Div. Polym. Chem.,Am. Chem. Soc. 31, 188–189.
Urry, D.W., Peng, S.Q., Xu, J. and McPherson, D.T. (1997) Characterization of Waters of Hydrophobic Hydration by Microwave Dielectric Relaxation, JACS 119, 1161–1162.
Urry, D.W. (1997) Physical Chemistry of Biological Free Energy Transduction as Demonstrated by Elastic Protein-Based Polymers J. Phys. Chem. B, 101(51), 11007–11028.
Pattanaik, A., Gowda, D.C. and Urry, D.W., (1991) Phosphorylation and Dephosphorylation Modulation of an Inverse Temperature Transition, Biochem. Biophys. Res. Comm. 178, 539–545.
Urry, D.W., Gowda, D.C., Peng, S.Q., and Parker, T.M. (1995) Non-linear Hydrophobic-induced pKa Shifts: Implications for Efficiency of Conversionto Chemical Energy, Chem. Phys. Letters, 239, 67–74.
Urry, D.W., and Peng, S.Q. (1995) Non-linear Mechanical Force-induced pKa Shifts: Implications for Efficiency of Conversion to Chemical Energy, J. Am. Chem. Soc. 117, 8478–8479.
Urry, D.W., Long, M.M., Harris, R.D., and Prasad, K.U. (1986) Temperature Correlated Force and Structure Development in Elastomeric Polypeptides: The Ile1 Analog of the Polypentapeptide of Elastin, Biopolymers 25, 1939–1953.
Prasad, K.U., Iqbal, M.A., and Urry, D.W. (1985) Utilization of I-Hydroxybenzotriazole in Mixed Anhydride Coupling Reactions, Int. J. Pept. and Protein Res. 25, 408–413.
Luan, C.H., Parker, T.M., Gowda, D.C., and Urry, D.W. (1992) Hydrophobicity of Amino Acid Residues: Differential Scanning Calorimetry and Synthesis of the Aromatic Analogues of the Polypentapeptide of Elastin, Biopolymers 32, 1251–1261.
Urry, D.W., Peng, S.Q., and Parker, T.M. (1992) Hydrophobicity-induced pK Shifts in Elastin Protein-Based Polymers, Biopolymers 32, 373–379.
Maniatis, T., Fritsch, E.F., and Sambrook, J. (1982) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Harbor, NY
McPherson, D.T., Xu, J., and Urry, D.W. (1996) Product Purification by Reversible Phase Transition Following E. coli Expression of Genes Encoding up to 251 Repeats of the Elastomeric Pentapeptide GVGVP, Protein Expression and Purification 7, 51–57.
Laemmli, U. K. (1970) Cleavage of Structural Proteins During the Assembly of the Head of Bacteriophage T4, Nature 227, 680–685.
Lee, C., Levin, A., and Branton, D. (1987) Copper Staining: A Five-Minute Protein Stain for Sodium Dodecyl Sulfate-Polyacrylamide Gels, Anal. Biochem. 166, 308–312.
Urry, D.W., and Luan, C.H. (1995) Proteins: Structure, Folding and Function, in Giorgio Lenaz (Vol. Ed.), Bioelectrochemistry: Principles and Practice, Birkhäuser Verlag AG, Basel, Switzerland, pp. 105–182.
Urry, D.W. (1991) Thermally Driven Self-assembly, Molecular Structuring and Entropic Mechanisms in Elastomeric Polypeptides, in P. Balaram and S. Ramaseshan, (eds.) Mol. Conformation and Biol. Interactions, Indian Acad. of Sci., Bangalore, India, pp. 555–583.
Urry, D.W., McPherson, D.T., Xu, J., Daniell, H., Guda, C., Gowda, D.C., Jing, N., and Parker, T.M. (1996) Protein-Based Polymeric Materials: Syntheses and Properties” in J.C. Salamone (ed.) The Polymeric Materials Encyclopedia: Synthesis, Properties and Applications, CRC Press, Boca Raton, pp. 7263–7279.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2002 Kluwer Academic Publishers
About this chapter
Cite this chapter
Urry, D.W. et al. (2002). ΔTt-Mechanism in the Design of Self-Assembling Structures. In: Self-Assembling Peptide Systems in Biology, Medicine and Engineering. Springer, Dordrecht. https://doi.org/10.1007/0-306-46890-5_23
Download citation
DOI: https://doi.org/10.1007/0-306-46890-5_23
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-7923-7090-1
Online ISBN: 978-0-306-46890-2
eBook Packages: Springer Book Archive