Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model
A hybrid blood–brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to...
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MDPI AG
2022-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/18/2801 |
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| author | Ajay Vikram Singh Vaisali Chandrasekar Peter Laux Andreas Luch Sarada Prasad Dakua Paolo Zamboni Amruta Shelar Yin Yang Vaibhav Pandit Veronica Tisato Donato Gemmati |
| author_facet | Ajay Vikram Singh Vaisali Chandrasekar Peter Laux Andreas Luch Sarada Prasad Dakua Paolo Zamboni Amruta Shelar Yin Yang Vaibhav Pandit Veronica Tisato Donato Gemmati |
| author_sort | Ajay Vikram Singh |
| collection | DOAJ |
| description | A hybrid blood–brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet–outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte–endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus. |
| first_indexed | 2024-03-10T00:26:55Z |
| format | Article |
| id | doaj.art-af1644f07d6a444db5815ea5adb5397c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:26:55Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-af1644f07d6a444db5815ea5adb5397c2023-11-23T15:32:35ZengMDPI AGCells2073-44092022-09-011118280110.3390/cells11182801Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP ModelAjay Vikram Singh0Vaisali Chandrasekar1Peter Laux2Andreas Luch3Sarada Prasad Dakua4Paolo Zamboni5Amruta Shelar6Yin Yang7Vaibhav Pandit8Veronica Tisato9Donato Gemmati10Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, GermanyDepartment of Surgery, Hamad Medical Corporation (HMC), Doha 3050, QatarDepartment of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, GermanyDepartment of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, GermanyDepartment of Surgery, Hamad Medical Corporation (HMC), Doha 3050, QatarDepartment of Vascular Surgery, University of Ferrara, 44121 Ferrara, ItalyDepartment of Technology, Savitribai Phule Pune University, Pune 411007, IndiaCollege of Science and Engineering, Hamad Bin Khalifa University (HBKU), Doha 24404, QatarDynex Technologies, 14340 Sullyfield Circle, Chantilly, VA 20151, USADepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyA hybrid blood–brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet–outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte–endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus.https://www.mdpi.com/2073-4409/11/18/2801blood–brain barriermicropatterningastrocyteneuropathologycalcium signaling |
| spellingShingle | Ajay Vikram Singh Vaisali Chandrasekar Peter Laux Andreas Luch Sarada Prasad Dakua Paolo Zamboni Amruta Shelar Yin Yang Vaibhav Pandit Veronica Tisato Donato Gemmati Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model Cells blood–brain barrier micropatterning astrocyte neuropathology calcium signaling |
| title | Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model |
| title_full | Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model |
| title_fullStr | Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model |
| title_full_unstemmed | Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model |
| title_short | Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model |
| title_sort | micropatterned neurovascular interface to mimic the blood brain barrier s neurophysiology and micromechanical function a bbb on chip model |
| topic | blood–brain barrier micropatterning astrocyte neuropathology calcium signaling |
| url | https://www.mdpi.com/2073-4409/11/18/2801 |
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