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A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow

Interstitial fluid pressure gradients and interstitial flow have been shown to drive morphogenic processes that shape tissues and influence progression of diseases including cancer. The advent of porous media microfluidic approaches has enabled investigation of the cellular response to interstitial...

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Autores principales: Wang, Hao, Lu, Jingming, Rathod, Mitesh, Aw, Wen Yih, Huang, Stephanie A., Polacheck, William J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539030/
https://www.ncbi.nlm.nih.gov/pubmed/37781136
http://dx.doi.org/10.1063/5.0165119
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author Wang, Hao
Lu, Jingming
Rathod, Mitesh
Aw, Wen Yih
Huang, Stephanie A.
Polacheck, William J.
author_facet Wang, Hao
Lu, Jingming
Rathod, Mitesh
Aw, Wen Yih
Huang, Stephanie A.
Polacheck, William J.
author_sort Wang, Hao
collection PubMed
description Interstitial fluid pressure gradients and interstitial flow have been shown to drive morphogenic processes that shape tissues and influence progression of diseases including cancer. The advent of porous media microfluidic approaches has enabled investigation of the cellular response to interstitial flow, but questions remain as to the critical biophysical and biochemical signals imparted by interstitial fluid pressure gradients and resulting flow on resident cells and extracellular matrix (ECM). Here, we introduce a low-cost method to maintain physiological interstitial fluid pressures that is built from commonly accessible laboratory equipment, including a laser pointer, camera, Arduino board, and a commercially available linear actuator. We demonstrate that when the system is connected to a microfluidic device containing a 3D porous hydrogel, physiologic pressure is maintained with sub-Pascal resolution and when basic feedback control is directed using an Arduino, constant pressure and pressure gradient can be maintained even as cells remodel and degrade the ECM hydrogel over time. Using this model, we characterized breast cancer cell growth and ECM changes to ECM fibril structure and porosity in response to constant interstitial fluid pressure or constant interstitial flow. We observe increased collagen fibril bundling and the formation of porous structures in the vicinity of cancer cells in response to constant interstitial fluid pressure as compared to constant interstitial flow. Collectively, these results further define interstitial fluid pressure as a driver of key pathogenic responses in cells, and the systems and methods developed here will allow for future mechanistic work investigating mechanotransduction of interstitial fluid pressures and flows.
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spelling pubmed-105390302023-09-29 A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow Wang, Hao Lu, Jingming Rathod, Mitesh Aw, Wen Yih Huang, Stephanie A. Polacheck, William J. Biomicrofluidics Regular Articles Interstitial fluid pressure gradients and interstitial flow have been shown to drive morphogenic processes that shape tissues and influence progression of diseases including cancer. The advent of porous media microfluidic approaches has enabled investigation of the cellular response to interstitial flow, but questions remain as to the critical biophysical and biochemical signals imparted by interstitial fluid pressure gradients and resulting flow on resident cells and extracellular matrix (ECM). Here, we introduce a low-cost method to maintain physiological interstitial fluid pressures that is built from commonly accessible laboratory equipment, including a laser pointer, camera, Arduino board, and a commercially available linear actuator. We demonstrate that when the system is connected to a microfluidic device containing a 3D porous hydrogel, physiologic pressure is maintained with sub-Pascal resolution and when basic feedback control is directed using an Arduino, constant pressure and pressure gradient can be maintained even as cells remodel and degrade the ECM hydrogel over time. Using this model, we characterized breast cancer cell growth and ECM changes to ECM fibril structure and porosity in response to constant interstitial fluid pressure or constant interstitial flow. We observe increased collagen fibril bundling and the formation of porous structures in the vicinity of cancer cells in response to constant interstitial fluid pressure as compared to constant interstitial flow. Collectively, these results further define interstitial fluid pressure as a driver of key pathogenic responses in cells, and the systems and methods developed here will allow for future mechanistic work investigating mechanotransduction of interstitial fluid pressures and flows. AIP Publishing LLC 2023-09-25 /pmc/articles/PMC10539030/ /pubmed/37781136 http://dx.doi.org/10.1063/5.0165119 Text en © 2023 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Regular Articles
Wang, Hao
Lu, Jingming
Rathod, Mitesh
Aw, Wen Yih
Huang, Stephanie A.
Polacheck, William J.
A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow
title A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow
title_full A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow
title_fullStr A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow
title_full_unstemmed A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow
title_short A facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow
title_sort facile fluid pressure system reveals differential cellular response to interstitial pressure gradients and flow
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539030/
https://www.ncbi.nlm.nih.gov/pubmed/37781136
http://dx.doi.org/10.1063/5.0165119
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