<p>The aim of the present study was to investigate the interaction between salts of fatty acids (FAS) and elastin. Absorption of fatty acids in elastin may affect the elasticity of elastin-containing tissue. Such phenomena could, for instance, be of relevance for the understanding of the formation of atherosclerotic plaque in blood vessel walls.<p>Chapter I gives a general introduction on the relevance of this study and an outline of the thesis. Furthermore, it contains information on the characteristics of both elastin and FAS.<p>In chapter 2, experiments are discussed that give insight into the absorption mechanism. Elastin from bovine ligamentum nuchae was exposed to solutions of FAS having hydrocarbon chain lengths varying between 12 and 16 carbon atoms. The amount absorbed was determined gravimetrically. The uptake of FAS can be described by a second order mechanism, in which the absorption rate depends on the concentration of FAS in solution and the number of absorption sites in elastin, and in which the desorption depends on the number of occupied sites. Competitive absorption experiments showed that the absorption rate constant decreases with increasing chain length. The binding of FAS is reversible. Therefore it is allowed to calculate the standard Gibbs energy, Δ <em><sub>abs</sub> G <sup>0</SUP></em> of the absorption process from the absorption isotherms. The affinity of the FAS for elastin is predominantly determined by hydrophobic interaction. The value for Δ <em><sub>abs</sub> G <sup>0</SUP></em> per CH <sub>2</sub> group in the FAS is -0.8±0.2kJ/mol. This is much smaller than Δ <em><sub>abs</sub> G <sup>0</SUP></em> for the transfer of CH <sub>2</sub> from an aqueous to a nonaqueous environment (-4kJ/mol). The difference may be explained by the fact that the FAS monomers that bind to elastin are released from micelles in solution. Although under the experimental condition of pH= 10 where the experiment have been carried out, the overall electric charge in elastin is negative, the contribution from the negatively charged head group of the FAS to Δ <em><sub>abs</sub> G <sup>0</SUP></em> is attractive and equal to about - 3k.J/mol. This suggests electrostatic attraction between FAS with positively charged groups, such as the desmosine and isodesmosine cross-links in elastin.<p>Binding of FAS is accompanied by co-absorption of salt (NaCl) and solvent in the elastin. The former results in an osmotic pressure between the elastin sample and the surrounding solution. This pressure increases as the salt concentration and/or the chain length of the FAS increases. The uptake of solution partly occurs to compensate for the electrostatic repulsion between the negatively charged groups of FAS in elastin. The swelling and, hence, the absorption of FAS is limited by the cross-linking of elastin. Due to the presence of OH- ions and absorbed FAS, degradation of elastin occurs, resulting in a decrease in cross-link density which, in turn promotes the uptake of more FAS. The rate of cross-link rupture is proportional to the osmotic pressure, both are larger for FAS with a longer chain. The inference is that the degradation of elastin is enhanced by the internal osmotic pressure.<p>Elastin is a network of randomly coiled polypeptide chains displaying rubber-elastic proper-ties. In chapters 3, 4 and 5 the influence of FAS on the rubber elasticity is studied.<p>In chapter 3, the change in elasticity modulus, which is the retractive force per unit cross-sectional area, is considered. The modulus depends on the number of cross- links per unit volume of elastin. Because of the degradation of elastin, caused by FAS uptake, the number of crosslinks and hence, the elasticity modulus decrease. The degradation rate increases with increasing chain length of the absorbed FAS. In addition, FAS may also change the rheological character of elastin. After a relatively long incubation time, depending on the water content and temperature, FAS may induce a change from a pure rubber-like into viscoelastic behaviour.<p>The influence of FAS on the conformational distribution of the chains in the network is discussed in chapter 4. The end-to-end length of the polypeptide chains does not change significantly upon FAS absorption, provided that the samples retain their rubber-elastic character. In the case of viscoelastic behaviour, no inference about the conformational properties of the chains could be made. Furthermore, the dependency of the conformational distribution on the temperature is hardly affected by FAS absorption. These results imply that the rotational freedom of the polypeptide chain is not significantly affected. The inference is made that the FAS molecules do not bind directly to the polypeptide units in the main chain, but rather to the (hydrophobic) side groups. It is also possible that FAS molecules bind to the cross- links, either through hydrophobic interaction with the alkyl groups and/or through electrostatic interactions with the positively charged quaternary ammonium group of the desmosine or isodesmosine units.<p>Upon lowering the temperature, the number of accessible conformations of the polypeptide chain decreases, which results in a rubberglass transition over a relatively narrow temperature range. The transition temperature (T <sub>g</sub> ) decreases with increasing water content in elastin. This can be explained by the reduction of intermolecular interactions and therefore by an increase of the rotational freedom at higher water content. As it was concluded that the rotational freedom of the polypeptide chains is not affected by absorption of FAS, no influence of FAS on T <sub>g</sub> is expected. In chapter 5, this expectation was confirmed. Binding of FAS does not directly influence the T <sub>g</sub> . However, since absorption of FAS causes swelling of the elastin network, and, therefore increases the uptake of water, binding of FAS indirectly causes a shift of T <sub>g</sub> towards lower values.<p>The most important conclusion concerning the interaction between FAS and elastin is that the direct influence of FAS on the elastic properties is very small. However, since FAS absorption is attended by swelling of the network and degradation of elastin, FAS absorption changes the rubber-elastic properties indirectly. The influence of the FAS is larger for longer chain length.
|Qualification||Doctor of Philosophy|
|Award date||24 Oct 1995|
|Place of Publication||S.l.|
|Publication status||Published - 1995|
- cardiovascular system