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<p>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 <i>α</i>2<i>β</i>1 and <i>α</i>5<i>β</i>1 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月27日

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  • Anna M. Nowicka,
  • Teresa Żołek,
  • Agata Kowalczyk,
  • Ireneusz P. Grudzinski

摘要

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.