Translating native protein behaviours from the nanoscale to the macroscale
Responsive protein complexes abound in Nature, often facilitating cell transport or adhesion, as a result of a specific cue from the surrounding environment. These stimuli can be chemical, mechanical, light or heat-induced and, often translate to a conformational or chemical change in the protein structure that drives the new behaviour permenantly or for a specific period of time (e.g., the length of the stimulus).
Mechanoresponsive proteins, at least from our point of view, are some of the most interesting protein complexes. Of particular interest, are catch bonding proteins that exhibit increased adhesive force as mechanical load is applied, although their rupture forces at equilibrium are rather weak. Their ability to adapt their mechanical properties in relation to mechanical cues is highly desirable for the design of responsive materials. However, translating these nanoscale behaviours of catch bond complexes into macroscale materials is not straightforward. We must first understand how the environemnt defines the mechanoresponsive behaiours and how this is effected by scaling and cooperativity between neighbouring complexes, as we move towards a material containing large numbers of protein complexes.
Funding from the Horizon 2020 MSCA Career Restart Fellowship (Zarah Walsh-Korb) has supported research in understanding how catch bonding complexes can be transplanted from the molecular scale to macroscale materials through single molecule (single molecule force spectroscopy), microscale (spinning disk microscopy) and macroscale (rheology) investigations. This work is underpinning further exploitation of catch bond cross-linked materials in impact resistant materials and as dynamic culture matrices for organoid culture. We are also interested in expanding the selection of mechanoresponsive proteins that can be transplanted into macroscale materials and understanding their biophysical properties as a function or environment, scaling and cooperativity.
Collaboration Partners:
Department of Chemistry, University of Basel; Dublin City University
Funding: