Lecture 24 - Mechanobiology II Flashcards
What is the lung on chip model?
Lung on chip - model to introduce organ on chip principal - facilitating in-vitro models of the future - PDMS based
What does it mean that lung-on-chip is PDMS-based?
When we say that a lung-on-a-chip is PDMS-based, we mean that the chip is made primarily of polydimethylsiloxane (PDMS), which is a type of silicone polymer.
Why is lung on chip PDMS-based (type of silicone polymer)?
- biocompatibility
- flexibility & transparency
- microfluidic properties
What is stress measured in?
θ (theta) or N/m^2
θ (theta) = F/A
F = force
A = area
What is strain measured in?
ε (epsilon) - unitless!
ε (epsilon) = ΔL/L₀
ΔL is the change in length,
L₀ is the original length of the material
What is Stiffness measured in?
E, stress over strain, N/m^2 = Pa)
E = θ (theta)/ε (epsilon)
At what rate does strain (length, volume) increase as stress (tension, pressure) increases?
Exponential
How do different tissues have different stiffness?
SOFT TISSUES - brain, embryo and breast
INTERMEDIATE TISSUES - liver, kidney, fat, dermis, lung
STIFF TISSUES - muscle, cartilage, bone
What does ECM (extracellular matrix) regulate?
stem cell differentiation
What occurs to cells in an environment with low stiffness?
cells become positive for neuro marker
What occurs to cells in an environment with medium stiffness?
cells become positive for myo marker (muscle cells)
What occurs to cells in an environment with high stiffness?
cells become positive for osteo marker
What is an example of how an increased stiffness can be used for diagnosis of diseased tissue?
Fibrotic liver displays shear stiffness of approximately 8 kPa, whereas a normal liver has a shear stiffness of approximately 2 kPa.
How can increased tissue stiffness assist intervention and therapeutic decisions?
- e.g. biopsy & treatment
- assessing prognosis and candidacy for treatment in patients with chronic liver disease
- saves patients that don’t need the discomfort and risk of complications associated with liver biopsy
What is one way a tumour can be identified?
- Tumour has a different stiffness form surrounding tissue, which allows a lump to be identified
- Surrounding tissues can become more stiff due to the expansion of tumour
What does a stiffened extracellular matrix promote?
the epithelial to mesenchymal transition and invasion
- During EMT (Epithelial-to-mesenchymal transition), epithelial cells lose their tight cell-to-cell junctions (such as tight junctions and adherens junctions), lose their polarity (the organization of the cell structure), and acquire the ability to move.
What can mechanical forces promote?
Tumour aggression
- increased epithelial to mesenchymal transition
- mechanical stress can disrupt cell adhesion (how cells stick together) -INVASION
- Shear stress (like fluid movement through blood vessels) can also increase the ability of tumor cells to invade through the ECM or surrounding tissue layers - INVASION
Describe the mechanical control of tumour cell fate
- Tension activates integrins (cell surface receptors that connect the cell to the ECM) and other mechanical sensors on the cell membrane, triggering intracellular signaling pathways like the Rho GTPase pathway, which controls cell shape, movement, and survival.
These signals can promote cell proliferation, survival, and invasion, allowing tumor cells to grow and spread. - High mechanical tension can push tumor cells to undergo EMT, where they lose their epithelial characteristics (like strong cell-cell adhesion) and adopt more mesenchymal properties (like increased mobility and invasiveness).
This transition is crucial for tumor cells to acquire the ability to migrate and invade surrounding tissues, which is a key step in metastasis.
What are 3 types of mechano-sensors?
- Piezo channels
- Integrins
- Caveolae
What are piezo-channels?
stretch-activated ion channels that have 38 transmembrane domains
What actually activated Piezo?
Piezo is mechanically activated by membrane/cortical tension
What role does actin play in piezo channels?
Lower forces needed to open the channel with actin, compared to without actin (almost double).
This means actin is supporting the force-channel connection.
