Mechanobiology Flashcards

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1
Q

What is mechanotransduction

A

Conversion of a physical force to a biochemical response

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2
Q

What is mechanosensing?

A

When a protein or cellular structure responds to a physical cue to initiate mechanotransduction. E.g a cell responding to surface stiffness

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3
Q

What is the signal cascade from mechonosensing?

A
  1. Mechanosensing with adhesion receptors
  2. Signal transduction
  3. Signal integration in the nucleus. Chromosome rearrangement
  4. Cellular response
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4
Q

How is blood pressure regulated?

A

Mechanoresponse to expanding/contracting blood vessels to keep blood pressure constant. When bloodflow is large, the diameter contracts to limit bloodflow to certain organs

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5
Q

Explain auditory mechanotransduction

A

Movement from sound bends cilia. Ion channels open and cause depolarisation.

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6
Q

How does lung on a chip imitate the gas exchange surface in lungs?

A

The system has a membrane flanked by endothelium and epithelium. A vacuum is introduced into the side chambers, stretching the cell layers, forming tight junctions

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7
Q

What are organs on chips used to study?

A

Inflammation, e.g adding TNFα
Neutrophils migrating from endothelial to epithelial layer to engulf bacteria

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8
Q

Why can nanoparticles enter through the alveoli epithelium?

A

Lungs can undergo mechanical stretching

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9
Q

What is the stiffness equation?

A

Stress / Strain (Pa)

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10
Q

What is the equation for stress?

A

F / A (Pa)

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11
Q

What is the equation for strain?

A

ΔL / L

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12
Q

What can increased tissue stiffness be an indicator of?

A

Chronic liver disease and cancer. The higher the stiffness in chronic liver disease, the higher the stage.

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13
Q

How is ECM stiffness usually altered around cancerous cells?

A

EMTs happen, so cell-cell adhesion is disrupted. Actomyosin contractility and cell-ECM adhesion increase

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14
Q

How are cellular mechanical forces measured?

A

Atomic force microscopy
Micropipette aspiration
Optical tweezers
Magnetic tweezers

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15
Q

Explain atomic force microscopy

A

A sensitive arm scans a sample and a laser beam is shone on it to show indentation.

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16
Q

What opens Piezo Channels?

A

Actin which pulls on the membrane or cytoskeleton

17
Q

What are piezo channels?

A

Mechanically activated ion channels, mainly Ca2+
38TM
Open under stress like a sliding door

18
Q

How does integrin act as a mechanosensor?

A

When integrins cluster into focal adhesions, thy bind to the ECM. Force in the ECM is exerted on talin, releasing its vinculin binding sites. Actin is connected to vinculin and changes the cytoskeleton.

19
Q

What happens when force is put on integrin?

A

Ligand binding is stronger, allowing a conformational change to take place

20
Q

How does caveolae act as a mechanosensor?

A

They flatten out upon stretching, preventing the cell tearing.
Filamin A mediates links to stress fibres and is regulated by Cav1

21
Q

What proteins shape caveolae?

A

Caveolins
Cavins
pacsin2

22
Q

What proteins regulate caveolae dynamics?

A

Dyn2
EDH2
Filamin A

23
Q

What happens when ECM stiffens?

A

Snail is upregulated which is a transcription factor of EMTs
Epithelial - Mesenchymal Transition and invasion.

24
Q

What can be used to inhibit EMTs?

A

Prevent ECM stiffening with TGF-β inhibitors
Integrin inhibitors
Inhibitors which interfere with ECM post translational modifications
Rho kinases to tackle signal transduction

25
Q

What does excessive YAP activation lead to?

A

Organ enlargement

26
Q

How is YAP regulated?

A

Downstream kinases

27
Q

What do YAP/TAZ and Yorkie regulate via the hippo pathway?

A

Proliferation
Cell survival
Cell competition
Stem cell maintenance
Metastasis
Regeneration

28
Q

What regulates nuclear localisaiton of the transcriptional regulator YAP?

A

ECM stiffness and cell size

29
Q

How can YAP activity be measured?

A

mRNA expression of its downstream molecules

30
Q

What is a positive regulator of myosin in the hippo pathway?

A

Rho kinases