Megan Greenfield

A self-assembly pathway to aligned monodomain gels

Aggregates of charged amphiphilic molecules have been found to access a structure at elevated temperature that templates alignment of supramolecular fibrils over macroscopic scales. The thermal pathway leads to a lamellar plaque structure with fibrous texture that breaks upon cooling into large arrays of aligned nanoscale fibres and forms a strongly birefringent liquid. By manually dragging this liquid crystal from a pipette onto salty media, it is possible to extend this alignment over centimetres in noodle-shaped viscoelastic strings. Using this approach, the solution of supramolecular filaments can be mixed with cells at physiological temperatures to form monodomain gels of aligned cells and filaments. The nature of the self-assembly process and its biocompatibility would allow formation of cellular wires in situ that have any length and customized peptide compositions for use in biological applications.

Tunable mechanics of peptide nanofiber gels.

The mechanical properties of self-assembled fibrillar networks are influenced by the specific intermolecular interactions that modulate fiber entanglements. We investigate how changing these interactions influences the mechanics of self-assembled nanofiber gels composed of peptide amphiphile (PA) molecules. PAs developed in our laboratory self-assemble into gels of nanofibers after neutralization or salt-mediated screening of the charged residues in their peptide segment. We report here on the gelation, stiffness, and response to deformation of gels formed from a negatively charged PA and HCl or CaCl(2). Scanning electron microscopy of these gels demonstrates a similar morphology, whereas the oscillatory rheological measurements indicate that the calcium-mediated ionic bridges in CaCl(2)-PA gels form stronger intra- and interfiber cross-links than the hydrogen bonds formed by the protonated carboxylic acid residues in HCl-PA gels. As a result, CaCl(2)-PA gels can withstand higher strains than HCl-PA gels. After exposure to a series of strain sweeps with increasing strain amplitude HCl- and CaCl(2)-PA gels both recover 42% of their original stiffness. In contrast, after sustained deformation at 100% strain, HCl-PA gels recover nearly 90% of their original stiffness after 10 min, while the CaCl(2)-PA gels only recover 35%. This result suggests that the hydrogen bonds formed by the protonated acids in the HCl-PA gels allow the gel to relax quickly to its initial state, while the strong calcium cross-links in the CaCl(2)-PA gels lock in the deformed structure and inhibit the gels ability to recover. We also show that the rheological scaling behaviors of HCl- and CaCl(2)-PA gels are consistent with that of uncross- and cross-linked semiflexible biopolymer networks, respectively. The ability to modify how self-assembled fibrillar networks respond to deformations is important in developing self-assembled gels that can resist and recover from the large deformations that these gels encounter while serving as synthetic cell scaffolds in vivo.

A Templating Approach for Monodisperse Self-Assembled Organic Nanostructures

The precise structural control is known for self-assembly into closed spherical structures (e.g., micelles), but similar control of open structures is much more challenging. Inspired by natural tobacco mosaic virus, we present the use of a rigid-rod template to control the size of a one-dimensional self-assembly. We believe that this strategy is novel for organic self-assembly and should provide a general approach to controlling size and dimension.

Buckled Membranes in Mixed-Valence Ionic Amphiphile Vesicles

Amphiphilic molecules can form closed-shell structures that are determined by competing attractive and repulsive forces. Since supramolecular shape has its roots in intermolecular interactions, the interplay of electrostatic, hydrophobic, and steric forces can generate nonspherical structures. Here we show that anionic and cationic amphiphiles of unequal charge can coassemble into small buckled vesicles and present a physical argument that explains this phenomenon. The strong electrostatic interaction between the +3 and -1 head groups increases the cohesion energy of the amphiphiles and favors the formation of two-dimensional, flat ionic domains on the vesicle surface, resulting in edges and a buckled shape.

Molecular crystallization controlled by pH regulates mesoscopic membrane morphology.

Coassembled molecular structures are known to exhibit a large variety of geometries and morphologies. A grand challenge of self-assembly design is to find techniques to control the crystal symmetries and overall morphologies of multicomponent systems. By mixing +3 and -1 ionic amphiphiles, we assemble crystalline ionic bilayers in a large variety of geometries that resemble polyhedral cellular crystalline shells and archaea wall envelopes. We combine TEM with SAXS and WAXS to characterize the coassembled structures from the mesoscopic to nanometer scale. The degree of ionization of the amphiphiles and their intermolecular electrostatic interactions are controlled by varying pH. At low and high pH values, we observe closed, faceted vesicles with two-dimensional hexagonal molecular arrangements, and at intermediate pH, we observe ribbons with rectangular-C packing. Furthermore, as pH increases, we observe interdigitation of the bilayer leaflets. Accurate atomistic molecular dynamics simulations explain the pH-dependent bilayer thickness changes and also reveal bilayers of hexagonally packed tails at low pH, where only a small fraction of anionic headgroups is charged. Coarse-grained simulations show that the mesoscale geometries at low pH are faceted vesicles where liquid-like edges separate flat crystalline domains. Our simulations indicate that the curved-to-polyhedral shape transition can be controlled by tuning the tail density in regions where sharp bends can form the polyhedral edges. In particular, the pH acts to control the overall morphology of the ionic bilayers by changing the local crystalline order of the amphiphile tails.