Enhancement of Endothelialization by Topographical Features Is Mediated by PTP1B-Dependent Endothelial Adherens Junctions Remodeling
| Autor: | Yusuke Toyama, Yi-Chin Toh, Pakorn Kanchanawong, Hui Ting Ong, Azita Gorji, Pearlyn Jia Ying Toh |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Chemistry
Collective cell migration 0206 medical engineering Combined use Biomedical Engineering Regulator Endothelial Cells Adherens Junctions 02 engineering and technology Protein tyrosine phosphatase 021001 nanoscience & nanotechnology 020601 biomedical engineering Cell Line Cell biology Biomaterials Adherens junction Crosstalk (biology) Cell Movement Endothelium Vascular VE-cadherin 0210 nano-technology Vascular graft |
| Zdroj: | ACS Biomaterials Science & Engineering. 7:2661-2675 |
| ISSN: | 2373-9878 |
| DOI: | 10.1021/acsbiomaterials.1c00251 |
| Popis: | Endothelial Cells (ECs) form cohesive cellular lining of the vasculature and play essential roles in both developmental processes and pathological conditions. Collective migration and proliferation of endothelial cells (ECs) are key processes underlying endothelialization of vessels as well as vascular graft, but the complex interplay of mechanical and biochemical signals regulating these processes are still not fully elucidated. While surface topography and biochemical modifications have been used to enhance endothelialization in vitro, thus far such single-modality modifications have met with limited success. As combination therapy that utilizes multiple modalities has shown improvement in addressing various intractable and complex biomedical conditions, here, we explore a combined strategy that utilizes topographical features in conjunction with pharmacological perturbations. We characterized EC behaviors in response to micrometer-scale grating topography in concert with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We found that the protein tyrosine phosphatase, PTP1B, serves as a potent regulator of EAJ stability, with PTP1B inhibition synergizing with grating topographies to modulate EAJ rearrangement, thereby augmenting global EC monolayer sheet orientation, proliferation, connectivity, and collective cell migration. Our data delineates the crosstalk between cell-ECM topography sensing and cell-cell junction integrity maintenance and suggests that the combined use of grating topography and PTP1B inhibitor could be a promising strategy for promoting collective EC migration and proliferation. |
| Databáze: | OpenAIRE |
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