Flow-induced mechano-modulation of intestinal permeability on chip

Area of Science:

• Biomedical Engineering
• Physiology
• Drug Development

Background:

• Intestinal transepithelial transport is crucial for nutrient and drug research.
• Microfluidic organ-on-chip platforms offer superior physiological replication compared to traditional in vitro models.
• The influence of fluid mechanical stimuli on gut barrier permeability remains largely unexplored.

Purpose of the Study:

• To investigate the effects of varying fluid shear stress on intestinal barrier permeability and functionality.
• To explore flow-induced changes in molecule transport, epithelial architecture, and barrier integrity.
• To inform the design of more biorelevant organ-on-chip models.

Main Methods:

• Development of an intestine-on-chip platform.
• Mechanical stimulation of intestinal cells with three distinct fluid shear stresses.
• Assessment of paracellular and transcellular transport.
• Impedance spectroscopy to measure epithelial barrier properties.

Main Results:

• Lower shear stress resulted in approximately 1.5 times higher and faster paracellular permeability.
• Higher shear stress led to approximately 3 times lower and delayed transcellular uptake.
• Impedance spectroscopy revealed altered tight junctional and bilayer resistance, and increased capacitance with varying mechanical stress.

Conclusions:

• Fluid shear stress acts as a significant mechano-modulator of intestinal epithelial transport.
• Mechanical forces influence both paracellular and transcellular pathways across the gut barrier.
• These findings are applicable to intestinal transport and other epithelial cell systems under physiological conditions.