Developing a Flow-Resistance Module for Elucidating Cell Mechanotransduction on Multiple Shear Stresses

Area of Science:

• Biomedical Engineering
• Cell Biology
• Mechanobiology

Background:

• Fluid shear stress is critical for cellular functions, tissue health, and disease development.
• Cells respond uniquely to varying shear stress levels, necessitating precise experimental control.
• Understanding cellular mechanotransduction is key to tissue engineering and disease research.

Purpose of the Study:

• To develop a novel flow-resistance module for precise control of fluid shear stress in microfluidic cell culture.
• To validate the module's performance using computational fluid dynamics and flow calibration.
• To investigate cellular responses to a wide range of physiologically and pathologically relevant shear stresses.

Main Methods:

• Development of a microfluidic flow-resistance module with three microchannels.
• Validation using computational fluid dynamics (CFD) simulations and flow calibration experiments.
• Analysis of gene expression, cytoskeletal remodeling, cell morphology, and YAP nuclear translocation under controlled shear stress.

Main Results:

• The flow-resistance module generated steady wall shear stresses from 0.06 to 11.57 dyn/cm².
• Cellular responses, including gene expression and YAP translocation, showed a clear increasing trend with elevated shear stress.
• The experimental platform demonstrated reliability in characterizing shear stress-induced cellular changes.

Conclusions:

• The developed flow-resistance module offers precise control over fluid shear stress for cell culture applications.
• This platform facilitates detailed investigation into cellular mechanobiology and responses to shear stress.
• The findings support the module's utility in characterizing cellular behavior under diverse shear stress conditions relevant to health and disease.