Sensitivity of peptide conformational dynamics in carbon nanotubes to directional mechanical forces

In living organisms, proteins and peptides are often under the influence of mechanical forces, especially in confined spaces such as membrane channels, ribosome exit tunnel, or proteasome gate. Due to the directional nature of proteins as polymers with distinct ends, forces have the potential to influence protein conformational dynamics in a direction-dependent manner. In this study, we employed force-probe molecular dynamics simulations to investigate the impact of pulling a peptide through a confined environment versus pushing it in the same direction. Our model involves a carbon nanotube and one of three decapeptides with varying amino acid sequences. The simulations reveal that the difference between pulling the C-terminus and pushing the N-terminus is relatively minor when considering the conformational ensembles of the peptides. The loading rate of the force probe and the amino acid sequence of the peptide play a more important role. However, the application of force to the peptide significantly influences the relative motion of the peptides with respect to the nanotube. Pulling the peptide results in a smoother translocation through the nanotube compared to pushing, although the internal conformational dynamics of the peptide add complexity in either case. Our findings shed light on how short peptides navigate confined spaces within the cellular environment, emphasizing the importance of force-probe simulation studies in understanding these processes.