Mechanically activated rupture of single covalent bonds: evidence of force induced bond hydrolysis.

We have used temperature-dependent single molecule force spectroscopy to stretch covalently anchored carboxymethylated amylose (CMA) polymers attached to an amino-functionalized AFM cantilever. Using an Arrhenius kinetics model based on a Morse potential as a one-dimensional representation of covalent bonds, we have extracted kinetic and structural parameters of the bond rupture process. With 35.5 kJ mol−1, we found a significantly smaller dissociation energy and with 9.0 × 102 s−1 to 3.6 × 103 s−1 also smaller Arrhenius pre-factors than expected for homolytic bond scission. One possible explanation for the severely reduced dissociation energy and Arrhenius pre-factors is the mechanically activated hydrolysis of covalent bonds. Both the carboxylic acid amide and the siloxane bond in the amino-silane surface linker are in principle prone to bond hydrolysis. Scattering, slope and curvature of the scattered data plots indicate that in fact two competing rupture mechanisms are observed

Force-dependent chemical kinetics of disulfide bond reduction observed with single-molecule techniques

The mechanism by which mechanical force regulates the kinetics of a chemical reaction is unknown. Here, we use single-molecule force–clamp spectroscopy and protein engineering to study the effect of force on the kinetics of thiol/disulfide exchange. Reduction of disulfide bonds through the thiol/disulfide exchange chemical reaction is crucial in regulating protein function and is known to occur in mechanically stressed proteins. We apply a constant stretching force to single engineered disulfide bonds and measure their rate of reduction by DTT. Although the reduction rate is linearly dependent on the concentration of DTT, it is exponentially dependent on the applied force, increasing 10-fold over a 300-pN range. This result predicts that the disulfide bond lengthens by 0.34 Å at the transition state of the thiol/disulfide exchange reaction. Our work at the single bond level directly demonstrates that thiol/disulfide exchange in proteins is a force-dependent chemical reaction. Our findings suggest that mechanical force plays a role in disulfide reduction in vivo, a property that has never been explored by traditional biochemistry. Furthermore, our work also indicates that the kinetics of any chemical reaction that results in bond lengthening will be force-dependent

A process evaluation of the NIDUS-Professional dementia training intervention for UK homecare workers

Introduction This process evaluation was conducted in parallel to the randomised controlled feasibility trial of NIDUS-Professional, a manualised remote dementia training intervention for homecare workers (HCWs), delivered alongside an individualised intervention for clients living with dementia and their family carers (NIDUS-Family). The process evaluation reports on (i) intervention reach, dose, and fidelity, (ii) contexts influencing agency engagement, and (iii) alignment of findings with theoretical assumptions about how the intervention might produce change. Methods We report proportions of eligible HCWs receiving any intervention (reach), number of sessions attended (dose; attending ≥4/6 main sessions was predefined as adhering), intervention fidelity and adherence of clients and carers to NIDUS-Family (attending all 6-8 planned sessions). We interviewed HCWs, managers, family carers and facilitators. We integrated and thematically analysed, at homecare agency level, qualitative interview and intervention recording data. Results 32/141 (23%) of eligible HCWs and 7/42 (17%) of family carers received any intervention; most who did adhered to the intervention (89% and 71%). Intervention fidelity was high. We analysed interviews with 20/44 HCWs, 3/4 managers and 3/7 family carers, and intervention recordings involving 32/44 HCWs. All agencies reported structural challenges in supporting intervention delivery. Agencies with greater management buy-in had higher dose and reach. HCWs valued NIDUS-Professional for enabling group reflection and peer support, providing practical, actionable care strategies, and increasing their confidence as practitioners. Conclusion NIDUS-Professional was valued by HCWs. Agency management, culture and priorities were key barriers to implementation; we discuss how to address these in a future trial

Mechanically Driven Activation of Polyaniline into Its Conductive Form

Mechanical treatment of polymers produces surface cations and anions which, as demonstrated here for the first time, can drive chemical reactions. In particular, it is shown that such a mechanical treatment transforms nonconductive polyaniline into its conductive form. These results provide a mechanical means of patterning conductive polymers and also coating small polymer objects with conductive polyaniline films preventing accumulation of static electricity