{Reference Type}: Journal Article
{Title}: Surface-driven first-step events of nanoscale self-assembly for molecular peptide fibers: An experimental and theoretical study.
{Author}: Forte G;Messina GML;Zamuner A;Dettin M;Grassi A;Marletta G;
{Journal}: Colloids Surf B Biointerfaces
{Volume}: 168
{Issue}: 0
{Year}: Aug 2018 1
{Factor}: 5.999
{DOI}: 10.1016/j.colsurfb.2018.01.016
{Abstract}: New experimental results are reported on the self-assembling behavior of EAK16-II, the first discovered ionic self-complementary peptide, incubated at ultralow concentration (10-6 M) at neutral pH onto differently charged surfaces. It is found that strongly negatively charged surfaces promote the self-assembly of flat, micrometer-long mono-molecular fibers of side-on assembled sequences, lying onto a continuous monolayer of flat-on EAK16-II molecules. These results suggest that the monomolecular EAK16-II self-assembly is driven by the peculiar matching condition between peptide and surface electrostatic properties. Molecular Mechanics simulations of the basic bimolecular interactions confirmed the experimental inferences, showing that the flat-on state is the most stable arrangement for two interacting EAK16-II sequences onto strongly negatively charged surfaces, where indeed EAK16-II β-sheet conformation is stabilized, while the weak electrostatic interactions with mildly charged substrates promote an "entangled" EAK16-II geometry. Molecular Dynamics simulations further showed that the mobility and diffusional freedom of the peptides from the surfaces are ruled by the relative strength of peptide-surface electrostatic interactions, so that desorption probability for the peptide sequences is negligible from strongly-charged surfaces and high from mildly-charged surfaces. Furthermore, it has been found that an oligopeptide sequence lying onto two flat-on EAK16-II molecules, gains a remarkable lateral mobility, while remaining weakly bound to the surface, thus allowing the further molecular self-alignment responsible for the micrometer-long fiber formation. The reported results pave the way to the understanding and control of the subtle peptide-surface structural motifs matching enabling the formation of micrometer-long, but nanometer-wide monomolecular fibers.