Mechanocatalytic Responsive Surfaces: Catalysis controlled by mechanical forces – MECHANOCAT

Smart materials which change their properties on command are currently of considerable interest because of their potential uses in a large variety of applications. Among all responsive materials developed so far, very few of them allow controlling a chemical reaction by a mechanical stress. Yet, nature offers numerous examples of chemo-mechanotransduction processes where macroscopic forces are transduced into a chemical reaction. One way that nature uses to achieve such transduction is through force-induced conformational changes in proteins. Inspired by nature, this project aims to design a new class of mechanocatalytic surfaces: catalytically active mechano-responsive materials based on alpha-helical peptides which play the role or constitute the backbone of artificial enzymes. alpha-helical peptides appear ideal candidates to design mechano-responsive enzymes because they are easy to design, can be rendered stable with a structure that should still respond to stretching and their catalytic "pocket" is directly related to the precise positioning of several specific amino-acids along the helix. These peptides will be covalently fixed through two points onto a silicone substrate. Stretching the substrate will change the relative positions between the chemical groups involved in the "enzymatic pocket" and thus affect their enzymatic activity and eventually their enantioselectivity. This project represents a new significant step in our effort to develop soft-mechanochemistry based materials, namely materials where the mechanotransduction process is based on macromolecular conformational changes. This is in marked rupture with the "conventional" mechanochemistry approach based on affecting chemical bonds by mechanical forces.
We will use two peptide-based catalysts as models. One system is an ester hydrolysis catalyst that mimics the well-known serine protease catalytic triad by introducing carboxylate (Asp), imidazole (His) and cyclodextrin (CD) groups at precise positions along the alpha-helix. The second example is provided by poly-L-leucine chains that adopt naturally alpha-helical conformations and which play the direct role of catalysts for the Julia-Colonna epoxidation reaction of electron deficient double bonds. In this case, it is well established that the poly-leucine a-helix conformation orients the olefins through specific hydrogen bonds leading to a high conversion and high stereochemical induction.
The goal of the MECHANOCAT project is to demonstrate the possibility to tune mechanically the catalytic activity of silicone substrates onto which are grafted the mentioned artificial enzymes and to investigate the possibility to control the conversion and the enantioselectivity of the catalytic reactions by stretching. The catalytic activities will be followed by UV-visible spectrophotometry and HPLC. Alpha-helical peptides whose structures are close to those of the enzyme models and bearing a pair of donor/acceptor fluorophores will be synthesized in order to realize Förster Resonance Energy Transfer experiments (FRET) in the non-stretched and stretched states: this will prove the strain induced peptide conformational change. Circular dichroism and IR spectroscopy will provide data about the unfolding of the peptides when stretched. The experiments will be supported by molecular dynamic simulations which will allow getting access to the molecular behaviour of the helices under stretching. In particular, we will ask the question on how the alpha-helices change conformation and how the relative positions of the chemical groups involved in the catalytic transition state evolve under stretching. This project is multi-field and interdisciplinary, involving three complementary partners, one focusing on peptides modification and characterization, one specialized in the surface science and the third partner focusing on the molecular dynamic simulations.