RAKSHIT, S. | Search bioRxiv

bioRxiv2022

Tip-links serve as force-pass filter to fulfil the role of gating-springs

Tip-links as gating-spring in the mechanotransduction in hearing is still a debate. While the molecular elasticity of individual tip-link proteins warrants its candidature, the apparent rigidity from the heterotetrameric tip-links assembly refutes the claim. Using force-clamp experiments and simulations, we report that the heterotetrameric assembly is the natural selection for the gating-springs. Tip-links follow slip-ideal-slip bonds with increasing force. While in slip, the complex dissociates monotonously, ideal-bond interface responds indifferently to various auditory inputs. Insensitivity to forces renders tip-links as low-force pass filter, characteristic of gating-spring. Individual tip-links, however, forms slip-catch-slip bonds under tension. While catch bonds turn stronger with force from loud sound, our Langevin dynamics indicated the transition from slip-catch to slip-ideal bonds as cooperative effect of the dimers of individual protein complexes in tip-links. From molecular dynamics, we deciphered the molecular mechanism of catch bonds and its importance in deafness.

biophysics↗

bioRxiv2022

Barrier-free liquid condensates of nanocatalysts as effective concentrators of catalysis

Molecular confinement of catalysts enhances the catalytic activity significantly. However, physicochemical barriers in traditional confinements restrict the free-passage of substrates/products. To obtain a barrier-free confinement of catalysts, here we explored the liquid-liquid phase separation. Using favourable ionic strength and crowding agents, we recruit the protein-inorganic-composites in phase separated liquid condensates from a solution. The phase separation propensity of these nanocomposites was seen to be independent of the native conformation of the component protein. Using standard catalytic oxidation-reduction reactions, we show that the close-proximity yet diffusive nature of catalysts in solution amplifies the homogeneous catalytic-efficiency of metal particles significantly. Overall, our work demonstrates the roadmap of using inorganic catalysts in homogeneous homogenous solution phase with amplified efficiency and longevity.

biophysics↗