Merg, A. | Search bioRxiv

bioRxiv2025

Vibrio cholerae adhesin-derived peptide mediates strong pull-off forces in aqueous high ionic strength environments

In this letter, the pull-off forces of adsorbed films of four Bap1-inspired peptides in various solvents were investigated on negatively charged mica substrates using the surface forces apparatus (SFA), complemented with dynamic light scattering (DLS) for characterizing the aggregation behavior of peptides in solution. Bap1-inspired peptides consisted of the 57 amino acid wild-type sequence (WT); a scrambled version of the WT used to investigate the impact of the primary amino acid sequence in pull-off forces (Scr); a ten amino acid sequence rich in hydrophobic content (CP) of the WT sequence, and an eight amino acid sequence (Sh1) that corresponds to the pseudo-repeating sequence in the 57 AA. SFA results showed remarkable pull-off forces for CP, particularly in the presence of salts: measured pull-off forces were 26.0 {+/-} 7.0 mN/m for no dwell-time and up to 42.0 {+/-} 8.8 mN/m when surfaces were left in contact for 30 minutes. DLS observations indicate that salts favor large peptide aggregation for all constructs (Hz > 1 {micro}m), as compared to milliQ (Hz {approx} 100-500 nm) water and DMSO (Hz {approx} 100 nm), resulting in heterogeneous peptide film thicknesses. This letter concludes with a comparison to the pull-off forces of mussel foot protein-inspired peptides reported in the literature.

biophysics↗

bioRxiv2021

Hidden structure in disordered proteins is adaptive to intracellular changes

Intrinsically disordered proteins and protein regions (IDPs) are essential to cellular function in all proteomes. Unlike folded proteins, IDPs exist in an ensemble of rapidly interchanging conformations. IDP sequences encode interactions that create structural biases within the ensemble. Such structural biases determine the three-dimensional shape of IDP ensembles and can affect their activity. However, the plasticity and sensitivity of IDP ensembles means structural biases, often measured in vitro, may differ in the dynamic and heterogeneous intracellular environment. Here we reveal that structural biases found in vitro in well-studied IDPs persist inside human-derived cells. We further show that a subset of IDPs are able to sense changes in cellular physical-chemical composition and modulate their ensemble in response. We propose that IDP ensembles can evolve to sense and respond to intracellular physicochemical changes, or to resist them. This property can be leveraged for biological function, be the underlying cause of IDP-driven pathology, or be leveraged for the design of disorder-based biosensors and actuators.

biophysics↗