SELFBIOLOGICS

Mimicry of biology supramolecular logics towards self-assembly of artificial components for life

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 Obiettivo del progetto (Objective)

'Whether a cell adheres to the extracellular matrix, or biological signals propagate within and between cells, highly selective interactions occur between the molecular ‘partners’ that materialize the process. Supramolecular chemistry studies the basic features of these interactions (knowledge) and their implementation for the design of non-natural systems (technology). This field bridges molecular chemistry and physics with biology, providing a interdisciplinary platform to understand biological structure (self-assembly) and function (recognition, reactivity and transport). Peptides that self-assemble in ordered nanostructures are a particular case of supramolecular chemistry. Peptides possess the biocompatibility and chemical diversity found in proteins, being particularly interesting for regenerative medicine and nanomedicine. Until now, peptide self-assembly systems have been studied individually. However, biological structures form in highly dense and heterogeneous molecular environments, such as the cytosol and extracellular matrix. The main scientific objective of this project is to recreate part of this complexity, by creating multi-component peptide self-assembly systems that form independent nano-assemblies in the same physical space. These systems will be used to provide technological solutions for the regeneration of ischemic neuronal tissues (artificial extracellular matrix) and the refined release of growth factors (capsules). These systems are also designed to be intermediate steps towards much more challenging future career objectives, namely cell-like bioreactors with the ability of protein production, self-maintenance or, even, self-replication. The beauty of this endeavor is that in the way towards such challenging scientific objectives, quite promising technological solutions can be derived, benefiting mankind health and welfare in ways that at the moment can just be painted with the faint colors of our imagination.'

Introduzione (Teaser)

Biological systems consist of cells in a complex extracellular matrix that plays an important but unclear role in peptide self-assembly. Studies have shed light on some mechanisms, supporting eventual self-assembly of biomimetic therapeutic structures.

Descrizione progetto (Article)

Proteins made up of long chains of peptides, in turn made up of sequences of amino acids, mediate most functions from the cellular level all the way up to the level of the organism. Not surprisingly, then, peptides and proteins have been the focus of many studies addressing their 3D structures, their formation and functionalisations, and their roles in health and disease.

However, very few have addressed the role of the complex intracellular and extracellular milieu in the self-assembly process. Such knowledge is necessary to exploit the potential of injectable molecular therapies that will self-assemble into functional peptides and fibrillar nanostructures, creating therapeutic scaffolds within the body.

The idea is to inject molecules that will replicate the biological features, both structural and functional, of the extracellular matrix. They will provide a temporary scaffold for tissue regeneration that will biodegrade and either be eliminated or reincorporated into the newly formed tissue once the process is initiated.

Such a therapy, the stuff of science fiction, requires excellent control over the self-sorting and co-assembly process. This in turn requires expertise in the role of the amino acid sequences of peptides in dictating molecular interactions. This was the focus of the EU-funded project 'Mimicry of biology supramolecular logics towards self-assembly of artificial components for life' (SELFBIOLOGICS).

Cell membrane lipids migrate between biomembranes. The peptides could thus feasibly change places, becoming water soluble and migrating from one nanostructure to reassemble in another. Scientists studied fast exchange dynamics in peptide self-assembly systems using fluorescence techniques to determine the role of amino acid sequences in the exchange rate. They then applied a high-resolution optical microscopy method (stochastic optical reconstruction microscopy) to study the molecular distribution along individual fibres during the exchange process.

Biomedicine is changing rapidly with therapies increasingly targeted at specific molecules and delivered to specific tissues or cellular systems. Minimally invasive techniques such as site-specific injection of molecules for self-assembling artificial extracellular matrices and tissue regeneration are expected to have tremendous socioeconomic impact. SELFBIOLOGICS has increased the necessary understanding of mechanistic and dynamic processes in peptide self-assembly, paving the road to futuristic therapies.