Self-Assembly of Model DNA-Binding Peptide Amphiphiles

Abstract

Peptide amphiphiles combine the specific functionality of proteins with the engineering convenience of synthetic amphiphiles. These molecules covalently link a peptide headgroup, typically from an active fragment of a larger protein, to a hydrophobic alkyl tail. Our research is aimed at forming and characterizing covalently stabilized, self-assembled, peptide-amphiphile aggregates that can be used as a platform for the examination and modular design and construction of systems with engineering biological activity. We have studied the self-assembly properties of a model DNA-binding amphiphile, having a GCN4 peptide as the headgroup and containing a polymerizable methacrylic group in the tail region, using a combination of small-angle X-ray scattering, small-angle neutron scattering, and cryo- transmission electron microscopy. Our results reveal a variety of morphologies in this system. The peptide amphiphiles assembled in aqueous solution to helical ribbons and tubules. These structures transformed into lamella upon DNA binding. In contrast with common surfactants, the specific interaction between the headgroups seems to play an important role in determining the microstructure. The geometry of the self-assembled aggregate can be controlled by means of adding a cosurfactant. For example, the addition of SDS induced the formation of spherical micelles.

Release of DNA from surfactant complexes induced by 2-hydroxypropyl-β-cyclodextrin

“…DNA was compacted by using a final CTAB concentration of 0.242 mM. At this concentration, all the DNA molecules were compacted and no coexistence between coils and globules was found [10]. The concentration of CD was varied in the decompaction studies whereas all the other parameters were kept constant.…”

“…The compaction is achieved through the formation of micelles in the vicinity of the DNA (sometimes referred to as surface micelles), that, being highly charged structures, induce ion correlation effects leading to the attraction of different parts of the DNA molecule [7]. The possibility of controlling the DNA morphology using self-assembled structures like surface micelles is very interesting and, in fact, it has already been used to improve the efficiency of other condensing agents, such as polyamines [8,9] and peptides [10,11]. DNA-cationic surfactant complexes can be 0141-8130/$ -see front matter © 2009 Elsevier B.V. All rights reserved.…”

De Novo Design of Bioactive Protein-Resembling Nanospheres via Dendrimer-Templated Peptide Amphiphile Assembly

“…Small peptide sequences isolated from parent proteins generally lose their secondary structure, which can be detrimental to their activity 25–26 . As observed with bZip, the peptide loses its native secondary structure but regains some degree of helical content after lipid conjugation, and exhibits greatly enhanced folding in the headgroup of micelles 5,27 . Interestingly, circular dichroism (CD) of di-C 16 -bZip showed that the PAs within the PRTNs possessed enhanced α-helical content, resembling that of micelles, with minima at 208 nm and 222 nm (Fig.…”

Surface Engineering Using Peptide Amphiphiles

“…In order for such practical applications to further advance the precise understanding of surface engineering principles, stability of assembled structures, biodistribution, and the cell-material interface created by peptide-based materials and living systems will be very important. Two key aspects of PAs' capabilities to control biological systems will be to control protein and nucleic acid function within and outside the cell 103,166,[189][190][191][192][193][194] and to three-dimensionally mimic the naturally occurring extracellular matrices 7,11,73,115,118,[195][196][197] if these two functions are combined and well defined, then some of the undefined components pertaining to biomedical applications, such as stem cell tissue engineering and targeted drug delivery, can incorporate more quantitative subcomponents. …”