Mechler - Bioinspired self-assembling nanostructures
Self-assembly is nature's way of building complex structures from molecular building blocks.
Cell membranes, silk fibres and proteins are examples of this process where final structure is the product of a multitude of second order interactions – individually weak, non-covalent bonds between adjacent molecules, the collective effect of which is a strong, stable superstructure.
Adapting the self-assembly process to the design of complex nanomaterials from unnatural building blocks requires the study of the natural processes and establishing design rules. This will eventually lead to the development of a "molecular lego" toolbox where the chemical building blocks can be selected at will to create complex nanostructures.
We study the principles of self-assembly in lipid membranes, peptide fibrillogenezis and peptide-membrane interactions, and apply the design rules in the development of biomimetic membrane platforms, novel peptide antibiotics and peptide based metamaterials.
Self-assembled phospholipid bilayers provide the core structure of cell membranes – the physical boundaries of cells and sub-cellular structures that preserve cell integrity while also serving as a platform for life functions related to metabolism, sensing and intercellular communication. Phospholipids, organised into a two-dimensional bilayer, provide the primary membrane structure.
We study the formation and physicochemical properties of phospholipid bilayers of various composition, with microscopic and microspectroscopic methods. Our aim is to describe the structural and chemical characteristics of such biomimetic membranes that are deterministic of their collective properties: phase transitions, tension, bending rigidity, as a function of composition and environmental factors. We create artificial biomimetic membranes on arbitrary surfaces to mimic the physiological environment of living cells, for applications in biophysics, while also furthering the fundamental understanding of lipid self-assembly.
Disruption of the integrity of cellular membranes underpins a broad spectrum of biophysical processes throughout the biological realm, from immunity to apoptosis. While this apparently simple process plays a variety of roles in nature, the mechanism of membrane disruption is not fully understood. One of the key processes of interest is membrane disruption by antimicrobial peptides. Antimicrobial peptides that provide innate immunity against pathogens in most living organisms disrupt the cytoplasmic membrane of pathogens, facilitate the efflux of essential ions, and thereby disrupt ionic homeostasis.
We study the molecular mechanism of antimicrobial peptide-membrane interaction. The focus is on identifying the factors contributing to the specificity and selectivity of these peptides towards pathogenic membranes. To achieve this goal, we study the role of lipid composition, peptide sequence, the physiological environment and temperature at various stages of the interaction, and the role these factors play in switching between disruptive and non-disruptive interaction pathways. The long term goal is to develop novel peptide-based broad spectrum antibiotics for last resort applications in the clinical setting.
Unnatural peptide-based fibrous materials and functional nanostructures
In collaboration with Monash researchers we have developed a unique β3 peptide based self-assembling platform that forms fibrous nanomaterials. These peptides fold into highly stable helices with a pitch of 3.0-3.1 amino acids, hence the side chains align in the larger polypeptides. The helical form is also remarkably stable even for short sequences and for a wide variation of amino acid side chain geometries and chemistries.
We study the factors affecting the self-assembly of these peptides, working towards implementing multiple self-assembly motifs and chemical "switches" to create either self-spun fibres, two dimensional arrays, or three dimensional metamaterials. The accessible sidechains offer easy pathways of chemical modification of these peptides, which we utilize to develop functional nanomaterials.
Meet the team
Zahra (Nadia) Saadatmand
Ahmed Jasim Mohammed Houri