Mechanically tuned lung-on-a-chip model: MECH-LoC
Chronic obstructive pulmonary disease (COPD) affects about 10% of the population, reducing the quality of life of affected patients.
Lung-on-a-chip models may help to tackle these diseases and propose new treatments.
This project is completed now. If interested, feel free to contact us.
Mechanically tuned lung-on-a-chip device: introduction
To better understand chronic obstructive pulmonary diseases, like emphysema or chronic bronchitis, and to screen potentially efficient drugs, appropriate lung models must be developed.
Based on 2D cell culture or living animal studies, the current models are pretty limited in physiological relevance.
Advances in microfluidics, particularly organ-on-chip, offer a powerful alternative to studying the lung membrane, providing a more realistic 3D cell culture environment and the potential to reduce the number of animal studies.
State-of-the-art lung-on-chip systems model the lung using two chambers, one filled with air and the other with liquid, separated by a semi-permeable membrane, typically a thin layer of flexible polymer such as polydimethylsiloxane (PDMS).
Cells are seeded on each side of this membrane to reproduce the liquid/air interface. Flanking vacuum chambers allow the membrane to be cyclically inflated to replicate breathing. This lung-on-chip system is suitable for measuring gas exchange, metabolite concentrations, or screening new drugs.
Mechanically tuned lung-on-a-chip device: our role
Lungs are constantly undergoing mechanical stress during breathing, making the elasticity of the membrane a crucial parameter for understanding lung diseases.
However, the polymer typically used to mimic the air / liquid membrane has an elastic modulus of up to one thousand times higher than its physiological equivalent and does not offer biological stimuli.
To advance lung-on-a-chip models, this project aims to control the membrane’s mechanical properties by adding fibrous matrix proteins (e.g., collagen and elastin). The fast and stable microfluidic flow control system will help to finely control membrane deformation and culture media.
The mechanical properties of this model lung membrane can be thus adapted to different disease phenotypes to be as relevant as possible in the development and screening of treatments.
As an alternative to conventional organ-on-a-chip materials such as PDMS, we also intend to use FlexdymTM, a polymer, to make our lung-on-a-chip devices. This fully biocompatible material makes the integration of cells into the system possible before chip assembly.
Mechanically tuned lung-on-a-chip device: results
1. Perfusable lung-on-chip assembly
2. Protein membrane physical characterization
3. Protein membrane mechanical characterization
Table 1. Elastic modulus values for protein membranes (elastin-collagen, EC 1:1) compared to PDMS spin coated films. Membrane thicknesses are indicated.
4. Characterization of protein membrane biocompatibility
Mechanically tuned lung-on-a-chip device: conclusion and perspective
Protein membranes’ sustained integrity and mechanical tunability illustrate their suitability as cell substrates for barrier models in perfusable microfluidic devices.
These studies reveal substantial opportunities to tailor membrane biomechanical activity to match physiological cell environments more closely and suggest the potential to define OOC devices with physiological and disease-matched mechanical profiles.
Read here the CORDIS interview with Dr. Lisa Muiznieks on her project at the Microfluidics Innovation Center, her goals, and her plans!
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 793749 (MECH-LoC).
If you want to learn more about modeling of the air-liquid interface in lung-on-a-chip applications, you find more information in the
Researcher
Dr. Lisa Muiznieks
Research Associate
- Post-Doc at Hospital for Sick Children (Canada), working on elastin structure and function
- PhD in Biochemistry (Sydney University, Australia)
- Bachelor of Science in Molecular Biology and Genetics (Sydney University, Australia)
Areas of expertise:
Structural biology, Protein elasticity, Lung-on-a-chip, Air-liquid interface.
