Chi‐Hao ‐H Luan

Hierarchical and Modulable Hydrophobic Folding and Self-assembly in Elastic Protein-based Polymers: Implications for Signal Transduction

When the hydrophobic (apolar) and polar moieties of elastomeric polypeptides are properly balanced, the polypeptides are soluble in water at lower temperatures but undergo folding and assembly transitions to increased order on raising the temperature. The temperatures, T t , and heats, ΔH t , of these inverse temperature transitions are determined by differential scanning calorimetry for a series of elastomeric polypentapeptides: poly(VPAVG), poly(IPAVG), poly(VPGVG), poly(IPGVG), poly[0.5(VPGVG),0.5(IPGVG)] and poly[0.82(IPGVG),0.18(IPGEG)] where V = Val, P = Pro, A = Ala, G = Gly, I = lle and E = Glu. On increasing the hydrophobicity as when replacing V(Val) by I(lle) which is the addition of one CH 2 moiety per pentamer, the temperature of the transition is lowered by 15 to 20°C and the heat of the transition is increased by more than one kcal/mole, for the above examples, by more than a factor of two. When differential scanning calorimetry thermograms are obtained on mixtures of poly(VPAVG) plus poly(IPAVG) or of poly(VPGVG) plus poly(IPGVG), it is found that the polypentapeptides self-separate, i.e., they de-mix, even though in the latter case the conformations have been shown to be essentially identical before and after their respective transitions. When the polymer, poly[0.82(IPGVG),0.18(IPGEG)], is studied as a function of pH, increasing the degree of ionization is found to increase the temperature and to decrease the heat of the transition such that, with the correct balance of I with the variable E(GluCOO − ), the values of T t and ΔH t can be made to approach those of poly(VPGVG). Acid-base titration studies indicate that less than one Glu(COO − ) in 200 residues can raise the value of T t by 25°C and decrease ΔH t by 90%. These and additional data are interpreted to mean that there exists an hierarchical hydrophobic folding, that the hierarchical hydrophobic folding can be modulated by changing the degree of ionization or by changes in a number of intensive variables, that changes in these intensive variables can be used to drive folding/unfolding-assembly/disassembly transitions under isothermal conditions, and that these unfolding/folding and disassembly/assembly transitions can be used to achieve signal transduction. This is called the ΔT t mechanism of free energy (signal) transduction.

Dielectric spectroscopy ofl-α-lysolecithin-packaged gramicidin A

Abstract The complex permittivities of l -α-lysolecithin in the absence and presence of the gramicidin A ion channel were measured over the temperature range 0-60°C and over the frequency range 1-1000 MHz. One dielectric relaxation/loss has been observed. It is located at 103.3 MHz (1.54 ns) for a micellar 0.4 M l -α-lysolecithin solution at 20°C, whereas it is shifted to 71.7 MHz (2.22 ns) for a lamellar l -α-lysolecithin-gramicidin A aqueous solution (0.4 M l -α-lysolecithin, 0.0308 M gramicidin A) at 20°C. The dielectric relaxation decreases and the relaxation time increases when gramicidin A is incorporated into l -α-lysolecithin. These dielectric changes are related, in part, to the micellar-to-lamellar lipid phase transition induced by the incorporation of gramicidin A into lysolecithin. We suggest that the diffuse rotational motion of the polar head group Of l -α-lysolecithin contributes to the dielectric relaxation/loss at around 100 MHz.