Suppressed Migration and Enhanced Cisplatin Chemosensitivity in Human Cancer Cell Lines by Tuning the Molecular Mobility of Supramolecular Biomaterials

Macromol Biosci. 2023 Feb;23(2):e2200438. doi: 10.1002/mabi.202200438. Epub 2022 Dec 16.

Abstract

Cancer cells recognize physical cues transmitted from the surrounding microenvironment, and accordingly alter the migration and chemosensitivity. Cell adhesive biomaterials with tunable physical properties can contribute to the understanding of cancer cell responses, and development of new cancer therapies. Previously, it was reported that polyrotaxane-based surfaces with molecular mobility effectively modulate cellular functions via the yes-associated protein (YAP)-related signaling pathway. In the present study, the impact of molecular mobility of polyrotaxane surfaces on the migration and chemosensitivity of lung (A549), pancreatic (BxPC-3), and breast cancer (MDA-MB-231) cell lines is investigated, and it is found that the cellular spreading of adherent A549 and BxPC-3 cells and nuclear YAP translocation are promoted on low-mobility surfaces, suggesting that cancer cells alter their subcellular YAP localization in response to molecular mobility. Furthermore, low-mobility surfaces suppress cellular migration more than high-mobility surfaces. Additionally, low-mobility surfaces promote the cisplatin chemosensitivity of each cancer cell line to a greater extent than high-mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces suppresses cellular migration and enhances chemosensitivity via the subcellular translocation of YAP in cancer cells. Biointerfaces based on polyrotaxanes can thus be a new platform for elucidating cancer cell migration and chemoresistance mechanisms.

Keywords: cancer cells; cellular migration; chemosensitivity; molecular mobility; polyrotaxane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Cisplatin* / pharmacology
  • Humans
  • Neoplasms*
  • Poloxamer
  • Tumor Microenvironment

Substances

  • Cisplatin
  • polyrotaxane
  • Biocompatible Materials
  • Poloxamer