Mehcanobiology Flashcards
What is mechanobiology?
Study of how physical forces changes in cell or tissue mechanics contribute to development, physiology and disease
What is mechanotransuction?
Conversion of a physical force to a biochemical response
What is mechanosensing?
When a protein or cellular structure responds to a physical cue to initiate mechanotransduction
What is are the steps building up to cellular response and their components?
- Mechanosensing: Adhesion receptors, membrane proteins/signalling
- Signal transduction: often along cytoskeleton
- Signal integration at nucleus: Chromatin rearrangement, nuclear pore opening
- Cellular response: Cell shape, fate, motility, growth
What is an example of mechanotransduction?
- Arteries increase with blood flow but capillaries cant cope so muscles contract to constrict the diameter again
- Cytoskeleton cell shape changes with fluid flow because cells counteract force that fluid flow is exerting
Describe the components of lung on a chip
- Mimic lungs on mechanical and cellular level
- Has fluid and air flow
- It has epithelial cells and flexible membranes with many channels
- Artificial membrane which contains small pores and the endothelium which mimics the blood vessels
- Vacuum on left and right side of the air/blood chamber, vacuum can be applied, stretched and released to reinact breathing
How is lung on a chip used to study lung inflammation?
- TNF is a cytokine involved in lung inflammation
- Once added, it can be seen that neutrophils get stuck to the endothelial layer due to the upregulation of adhesion receptors
- They migrate towards the epithelial layer over time through pores
How is lung on a chip used to study lung infection?
- Adding E.coli on the epithelial layer
- Bacteria secretes factors inducing TNF
- Leads to neutrophils being accumulated
- Neutrophil migration through endothelial and epithelial layer and engulfs the bacteria
What is a neutrophil?
A type of white blood cell involved in the immune systems response to inflammation and infection
How is lung on a chip used to study mechanical stretching as a result of nanoparticles?
- Gas particles applied within air channel of lungs
- These particles initiate inflammatory response: adhesion of neutrophils, immobilisation etc.
- Mechanical stretching mimics the breathing
- See an increase in iCAM1 expression which is involved in facilitating the adhesion of immune cells in the inflammatory response
Why are organ on chip experiments good?
- Can be used to reduce animal experiments as human cells can be used on the chip
What is the equation for stress?
Force/Area
(Pa)
What is the equation for strain?
Change in length/ Original length
No units
What is the equation for stiffness?
Stress/Strain
(kPa)
- Plotting stress against strain can give u info about the defined properties of a material
Give some examples of soft, intermediate and stiff tissues in the body
Soft: Brain, breast
Intermediate: Liver, Kidney, Lung
Stiff: Cartilage, bone
How can stiffness be measured?
By indentation, looking at the force applied and the depth of indentation into plastic
How is stiffness relevant in differentiation?
- Human stem cells can develop into bone, muscle and brain cells
-Stiffness can steer differentiate - When generating stem cells, provides information that neurons for example need a softer surface than plastic for in vitro experiments
How can ultrasounds be used to measure the stiffness of organs?
- Looks at speed of sound and how fast its being transmitted which is proportional to stiffness
- Non invasive
Give examples of two diseases where there is increased stiffness in the organs
- Fibrotic diseased liver
- Chronic liver disease
How is cancer associated with tissue stiffening ?
- Lump like structures often detected by the patients
- Tumour tissue is stiffer than surrounding healthy tissue
- Stiffness can go up to 8kPa
- Tumour is exerting force on to adjacent healthy tissue, modifying the healthy tissue
Why is a tumour stiffer than a normal cell? LEARN
- Cells more tightly packed
- Tumour cells and fibroblasts (tumour-activating) are excreting much more extracellular matrix than normal *
Cross-linking of ECM*
Desnity of tumour cell *
What mechanosensors detect pressure in the cell?
- Piezo channels
- Integrins
- Caveolae
How do piezo channels work?
- Ion channels which respond to stretch (mechosensitive)
- When lateral tension to the membrane is applied (pulled on either side) pore opens leading to the influx of extracellular Ca2+ and transducing mechanical signals into electrical and chemical signals in the cell.
- actin filaments is what pulls the membrane
- F-actin facilitates opening of the pore
How do integrins work?
- Mechanoreceptor, transmembrane, links cells with the ECM
- Activated through ‘inside out’ signalling, phosphorylation on the inside signals for integrins to engage with the ECM
- F-actin connects to integrins through Talin and Vinculin
- Vinculin binds when the actin-myosin (connected to integrins through talin) applies a force and pulls, unfolding a binding site for vinculin enhacing the F-actin connection
- So integrins connect with intracellular matrix (F-actin) on one side and ECM on the other
