Davide M. Marini

Design of Nanostructured Biological Materials Through Self-Assembly of Peptides and Proteins

Several self-assembling peptide and protein systems that form nanotubes, helical ribbons and fibrous scaffolds have recently emerged as biological materials. Peptides and proteins have also been selected to bind metals, semiconductors and ions, inspiring the design of new materials for a wide range of applications in nano-biotechnology.

Targeted cytosolic delivery of cell-impermeable compounds by nanoparticle-mediated, light-triggered endosome disruption.

Nanoparticle (NP)-mediated drug delivery typically relies on cargo release to occur passively or in response to environmental stimuli. Here we present a delivery method based on light-activated disruption of intracellular vesicles after internalization of biofunctionalized mesoporous silica nanoparticles loaded with cargo. This method combines the power of targeted delivery with the spatiotemporal control of light activation. As an example, we delivered a cell-impermeable fluorescent compound exclusively to the cytosol of multidrug resistant cancer cells in a mixed population.

Supramolecular structure of helical ribbons self-assembled from a β-sheet peptide

We have investigated the supramolecular structure of helical ribbons formed during self-assembly of a β-sheet peptide using computer simulation. We tested a wide range of molecular packing geometries consistent with the experimental dimensions to identify the most stable structure, and then systematically changed the helical geometry to investigate its energy landscape. The effect of pH was incorporated by scaling the amount of charge on the side chains based on the electrostatic double layer theory. Our results suggest that these left-handed helical ribbons are comprised of a double β-sheet and that the experimentally measured dimensions correspond to a local energy minimum. Side chain interactions are found to be critical in determining the stability and curvature of the helix. Our approach has general applicability to the study of self-assembled nanostructures from β-sheet peptides where high resolution data are not yet available.

Supramolecular structure of a helical ribbon peptide self-assembly

We have studied the supramolecular structure of nanometer scale helical ribbons observed in the self-assembly of beta-sheets forming peptide KFE8 (amino acid sequence: FKFEFKFE). By running molecular dynamics simulations on a wide range of possible combinations of single and double layer beta-sheet ribbons, we identified the most stable structure. The effect of solution pH was incorporated by scaling the charge on sidechains based on electrostatic double layer theory. Our results suggest that the helical ribbon is comprised of a double beta-sheet having multiple local energy minima at different pitch values. Electrostatic interactions between charged sidechains are found to be crucial in determining the curvature and elasticity of the helix, which suggests that the helical shape depends on the solution properties. Our approach has general applicability to studying helices made of beta-sheet forming peptides with various amino acid sequences.

Nanoscale helical ribbons from self-assembly of a /spl beta/-sheet peptide

We have investigated the intermediate structures in the self-assembly of a peptide (of sequence FKFEFKFE) designed with alternating polar and nonpolar amino acids. Self-assembly was followed over time using atomic force microscopy, transmission electron microscopy and circular dichroism. Molecular dynamics simulations suggest that these intermediates are left-handed double helical /spl beta/-sheets. These findings have implications in the study of protein conformational diseases and in the molecular design of materials.