Structural and mechanistic insights into α2β1 and α5β1 integrin targeting by bioengineered extracellular vesicles originating from lung cancer cells.

Integrins are transmembrane receptors that mediate bidirectional signaling across the plasma membrane and play a crucial role in tumor progression, metastasis, and cellular communication. In this study, we performed a comparative structural and biophysical analysis of the PTHTRWA-functionalized extracellular vesicles (PTHTRWA-EVs) interacting with α2β1 and α5β1 integrins to investigate the molecular determinants underlying selective recognition. Surface plasmon resonance experiments were used to characterize multivalent bioengineered EVs --- integrin binding under physiological conditions, while molecular dynamics simulations provided residue-level insight into local ligand-receptor interaction patterns and conformational preferences. These results indicate that PTHTRWA binding is associated with local conformational rearrangements consistent with stabilization of an open-like binding geometry at the integrin interface. Together, these complementary approaches highlight the potential of PTHTRWA-functionalized EVs as a platform for targeted drug delivery and cancer diagnostics.