Cell shape-dependent shear stress on adherent cells in a micro-physiologic system as revealed by FEM

Area of Science:

• Cellular biomechanics
• Fluid dynamics
• Biomedical engineering

Background:

• Flow-induced shear stress influences cellular biochemical signaling and mechanical responses.
• Understanding shear stress in microfluidic devices is crucial for cell culture and biological studies.

Purpose of the Study:

• To develop and validate a finite element method (FEM) model for determining flow-induced shear stress on adherent cells in a micro-scaled reaction chamber.
• To investigate the influence of key parameters (cell shape, density, shear modulus, fluid velocity) on shear stress.
• To experimentally assess the impact of shear stress on cell metabolic activity and morphology.

Main Methods:

• Development of a finite element method model for fluid flow simulation in a micro-chamber.
• Computational analysis of parameters including cell shape, density, shear modulus, and fluid velocity.
• Experimental validation of computational fluid flow simulations.
• In vitro experiments on L929 mouse fibroblast cells to assess metabolic activity and shape changes under varying flow conditions.

Main Results:

• Cell shape is a critical factor, with rounded cells experiencing higher shear stress than elongated cells.
• Single cells or cells in sparse cultures are subjected to greater shear stress compared to confluent monolayers.
• Stress concentrations occur at areas of high cell curvature.
• Experimental results validated the computational model's predictions.
• Threshold shear stress values for continuous flow are not directly applicable to quasi-static, intermittent flow conditions.

Conclusions:

• The developed FEM model accurately predicts flow-induced shear stress on adherent cells in microfluidic systems.
• Cellular morphology and arrangement significantly modulate shear stress distribution.
• Distinct flow patterns (continuous vs. intermittent) necessitate different stress threshold considerations for cellular response.
• This study provides valuable insights for designing microfluidic devices and optimizing cell culture conditions.