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Designing Microfluidic Devices for Studying Cellular Responses Under Single or Coexisting Chemical/Electrical/Shear Stress Stimuli
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Multiplexed Fluid Flow Device to Study Cellular Response to Tunable Shear Stress Gradients
Maggie A Ostrowski1, Eva Y Huang1, Vinay N Surya1
1Department of Chemical Engineering, Stanford University, 443 Via Ortega, Stanford, CA, 94305, USA.
Annals of Biomedical Engineering
|November 22, 2015
Summary
Lymphatic endothelial cells uniquely migrate against fluid flow when exposed to wall shear stress gradients. This response involves microtubule organizing center relocation, highlighting flow
Area of Science:
- Cell Biology
- Biophysics
- Fluid Dynamics
Background:
- Endothelial cells (ECs) in blood and lymphatic vessels experience wall shear stress (WSS).
- Sensing spatially varying WSS by mammalian cells is poorly understood due to limited experimental tools.
- Understanding cellular responses to WSS gradients is crucial for vascular biology.
Purpose of the Study:
- To develop a novel device for exposing cells to controlled WSS gradients.
- To investigate the migratory response of various cell types to WSS gradients.
- To elucidate the mechanisms underlying cellular responses to fluid flow.
Main Methods:
- Development of a 6-well impinging flow chamber for controlled WSS gradients.
- Time-lapse live cell imaging to observe cellular migration and organelle dynamics.
- Screening of canonical signaling pathways involved in the migratory response.
Main Results:
- Lymphatic microvascular ECs uniquely migrated upstream against the direction of flow.
- Microtubule organizing center repositioned upstream of the nucleus in response to WSS gradients.
- Other investigated cell types (umbilical vein ECs, fibroblasts, epithelial cells) did not exhibit upstream migration.
Conclusions:
- Wall shear stress magnitude and spatial gradients significantly influence cellular responses to fluid flow.
- Lymphatic ECs possess a unique upstream migratory behavior mediated by cytoskeletal rearrangements.
- The developed impinging flow chamber is a valuable tool for studying mechanotransduction in various cell types.

