crc press - E-Lib FK UWKS

Interactions of Cell-Penetrating Peptides with Membranes 175
FIGURE 8.5 Variation of the transition surface pressure as a function of the lipid molar
fraction (x P). The data are provided from Figure 8.1. The dashed vertical bar shows the limits
of the phase transitions. (Adapted from Van Mau, N. et al., J. Membr. Biol., 167, 241, 1999.
With permission.)
The phase separation deduced by analysis of the compression isotherms was
confirmed by direct observations using AFM imaging on transferred monolayers.
Figure 8.6 reveals strong changes on lipid-embedded particles when the peptide
molar ratio is varied. The clear domains (Figure 8.6C) confirm the existence of
peptide-induced phase separation; evolution of the shape of the particle is in accordance
with a conformational change of the peptide with formation of mixed particles
compatible with the FTIR observations.
8.2.2.8.2 Influence of the Sequence
Cell positioning: membrane associated or nuclear — Within the SP–NLS peptides
(Table 8.1) and FP–NLS (Table 8.2), several variants have been synthesized. While
single K to S mutations in the NLS sequences do not modify the final nuclear
localization, removal of the W-S-Q-P linker can strongly modify the final cellular
localization. For the SP–NLS peptides, the presence of this linker has no influence
on final localization, 47 however, its absence in the FP-NLS series leads to a peptide
that has a membrane-associated localization. 48 The origin of these different behaviors
according to the nature of the hydrophobic sequence is still not clear and no rational
explanation has been provided up till now, although some preliminary data suggest
that the peptide–peptide interactions involving the N-terminal hydrophobic domain
could play an important role.
Comparison between FP- and SP-NLS: a possible role of the conformation — A comparative
study of peptides of the two series made on model membrane systems also
provided some unexpected information. Using vesicles made of pure phospholipids