The present work focuses on the computational study of the structural micro-organization of hydrogels based on collagen-like peptides (CLPs) in complex with Rose Bengal (RB). In previous studies, these hydrogels computationally and experimentally demonstrated that when RB was activated by green light, it could generate forms of stable crosslinked structures capable of regenerating biological tissues such as the skin and cornea. Here, we focus on the structural and atomic interactions of two collagen-like peptides (collagen-like peptide I (CLPI), and collagen-like peptide II, (CLPII)) in the presence and absence of RB, highlighting the acquired three-dimensional organization and going deep into the stabilization effect caused by the dye. Our results suggest that the dye could generate a ternary ground-state complex between collagen-like peptide fibers, specifically with positively charged amino acids (Lys in CLPI and Arg in CLPII), thus stabilizing ordered three-dimensional structures. The discoveries generated in this study provide the structural and atomic bases for the subsequent rational development of new synthetic peptides with improved characteristics for applications in the regeneration of biological tissues during photochemical tissue bonding therapies.

Protein–protein interactions (PPIs) play a central role in regulating cellular processes. However, the identification and characterization of senescence-associated PPIs remain challenging. In this study, we developed and evaluated an integrative methodology based on selective proteomics to identify PPIs associated with cellular senescence induced by TMPRSS11a. We started from isolated proteins that co-immunoprecipitated with TMPRSS11a and were subsequently identified by mass spectrometry. Building on this dataset, we implemented a workflow combining selective proteomics, structural bioinformatics, and experimental validation. Using this approach, we investigated the interaction between the transmembrane serine protease TMPRSS11a and the chaperone HSPA8. Structural bioinformatics analyses were performed to identify potential residues involved in the interaction interface, and the proximity of the TMPRSS11a–HSPA8 complex was evaluated using an in vitro proximity ligation assay. Our results provide evidence for an interaction between TMPRSS11a and HSPA8 and suggest its association with an enhanced senescence response. Overall, this study presents a workflow to investigate senescence-associated PPIs from proteomics-derived candidate proteins.