Lecture 26 Mechanobiology II Flashcards
A smaller change in length, when high stress is applied to a material means what?
The material is stiffer giving a higher value
What is the stiffness of plastic dishes relative to bone and brain?
Plastic dishes - very stiff = 100kPa
Bone - stiff
Brain - soft (0.3kPa)
What is the implication of the plastic dish stiffness?
Mechanically very non-physiological
How can tissue stiffness be mimicked?
Hydrogels - these can be tuned to different stiffnesses
How well do cells grow on hydrogel?
Not very well
What is added to the top of the hydrogel
A layer of ECM e.g. collagen or fibronectin to help the cells grow
What do ECM and tissue stiffness regulate
Stem cell differentiation
What differentiates into a range of cell types depending on the stiffness of the material
Human multipotent stem cells (MSCs)
What do MSCs differentiate into if grown on soft environment?
Neurons
What do MSCs differentiate into if grown on hard environment?
Bone
What do MSCs differentiate into if grown on intermediate environment?
Muscle
Where are MSCs exploited?
Stem cell therapy
How is stiffness and disease linked?
Where is this shown?
Increased stiffness can indicated and be used to diagnose diseased tissue
e.g. fibrotic liver is stiffer - clinician may palpate liver/abdomen
In chronic liver disease, what is there a correlation between?
Liver stiffness and stages of chronic liver disease
How is liver stiffness measured? Why?
Elastogram
- non invasive vs biopsy
- assesses patients prognosis and candidacy for treatment
- spare discomfort/risk complications of biopsy
How is breast cancer detected and why?
Self-examination
Since breast tissue is relatively soft (1kPa), tumours will be easily palpable, as they are stiffer than the surrounding environment.
What happens as a tumour proliferates?
- As a tumour proliferates, it exerts a mechanical force upon the surrounding tissue.
- Newton’s 3rd Law stipulates that this results in the same mechanical force being directed from surrounding tissue upon the tumour (for every action there is an equal and opposite reaction).
- This will change the properties of the ECM, making it stiffer than the tissue surrounding it. This occurs through changes to ECM secretions, amount of ECM secreted and cross-linking of ECM.
- It alters the signal transduction pathway and actin cytoskeleton by changing the actomyosin contractility of the surrounding cells, altering gene expression
- Interactions with the ECM is change as cell-cell adhesion is changed
- The epithelial monolayer is disturbed due to EMT
- Increased cell-ECM adhesion
Stiffness seems to contribute to what?
The change in stiffness seems to be part of the disease process and contributes to it’s progression, particularly to metastasis.
How does the ECM stiffness link to metastasis
The stiffer the ECM, the easier tumour metastasis will be.
What 5 techniques measure cellular mechanical forces?
- atomic force microscopy
- micropipette aspiration
- optical tweezers
- magnetic tweezers
- uniaxial stretcher
what does atomic force microscopy measure?
designed to measure local properties, such as height, friction, magnetism, with a probe
In atomic force microscopy, a cantilevered probe is used to indent the cell. A laser on-top of the cantilever will change the reflection angle of the laser beam (measured by a detector) to a degree which depends on the depth of the indentation. The identation is correlated to a specific force.
what does micropipette aspiration measure?
- Measures membrane tension by measuring the membrane potential (membrane clamping)
what are optical tweezers?
Use a highly focused laser beam to move a bead that will bind to the membrane to apply an attractive or repulsive force that to the cell/molecule
what do magnetic tweezers measure?
- Measure the tensile strength or the force generated by molecules
