Biologically Inspired Molecular Adhesives towards Multifunctional Biomaterials and Microreactors

Recombinant proteins, including enzymes and antibodies, have revolutionized many sectors of biochemistry and biotechnology.

In this project I propose a groundbreaking technology to control the supramolecular assembly of proteins in space and time to better mimic cellular organization and create a next generation of protein “living” materials for biocatalysis and medicine.

The core idea is to mimic cellular multiprotein assemblies and microreactors on the bench, by compartmentalizing multiple proteins in space.

Increasing evidence indicates that cells can coordinate crucial functions by forming membrane-less compartments via liquid-liquid phase separation of proteins and nucleic acids.

Most of the proteins involved in this process consist of globular regions and disordered domains, which are enriched in specific aminoacids and pilot highly controlled self-assembly.

In this project we will conjugate functional globular proteins with sequences that mimic the disordered biological domains and act as “molecular Velcros”, thereby coupling biochemical functions with phase separation in space and time.

Using a combination of microfluidic technology and in silico analysis, we will develop sequences capable to control not only the dynamic process of phase separation but also the phenotype of the resulting compartments, including selective recruitment of molecules, physical properties and response to specific switches.

This project will deliver adaptive compartments with unprecedented control of composition, environment, biochemical function and stimulus-responsiveness, going towards the development of networks of open microreactors, superior enzymes for green chemistry as well as smart materials for drug delivery.

Moreover, the results will generate new knowledge on natural supramolecular structures that are associated with both functional biology and aberrant aggregates involved in devastating disorders such as Alzheimer’s and Parkinson’s disease.