Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cell and molecular extras > Lecture 26 Mechanobiology II > Flashcards

Lecture 26 Mechanobiology II Flashcards

1
Q

A smaller change in length, when high stress is applied to a material means what?

A

The material is stiffer giving a higher value

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the stiffness of plastic dishes relative to bone and brain?

A

Plastic dishes - very stiff = 100kPa
Bone - stiff
Brain - soft (0.3kPa)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the implication of the plastic dish stiffness?

A

Mechanically very non-physiological

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How can tissue stiffness be mimicked?

A

Hydrogels - these can be tuned to different stiffnesses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How well do cells grow on hydrogel?

A

Not very well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is added to the top of the hydrogel

A

A layer of ECM e.g. collagen or fibronectin to help the cells grow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What do ECM and tissue stiffness regulate

A

Stem cell differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What differentiates into a range of cell types depending on the stiffness of the material

A

Human multipotent stem cells (MSCs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What do MSCs differentiate into if grown on soft environment?

A

Neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What do MSCs differentiate into if grown on hard environment?

A

Bone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do MSCs differentiate into if grown on intermediate environment?

A

Muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where are MSCs exploited?

A

Stem cell therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is stiffness and disease linked?

Where is this shown?

A

Increased stiffness can indicated and be used to diagnose diseased tissue
e.g. fibrotic liver is stiffer - clinician may palpate liver/abdomen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

In chronic liver disease, what is there a correlation between?

A

Liver stiffness and stages of chronic liver disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is liver stiffness measured? Why?

A

Elastogram

  • non invasive vs biopsy
  • assesses patients prognosis and candidacy for treatment
  • spare discomfort/risk complications of biopsy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is breast cancer detected and why?

A

Self-examination
Since breast tissue is relatively soft (1kPa), tumours will be easily palpable, as they are stiffer than the surrounding environment.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What happens as a tumour proliferates?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Stiffness seems to contribute to what?

A

The change in stiffness seems to be part of the disease process and contributes to it’s progression, particularly to metastasis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does the ECM stiffness link to metastasis

A

The stiffer the ECM, the easier tumour metastasis will be.

20
Q

What 5 techniques measure cellular mechanical forces?

A
  • atomic force microscopy
  • micropipette aspiration
  • optical tweezers
  • magnetic tweezers
  • uniaxial stretcher
21
Q

what does atomic force microscopy measure?

A

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.

22
Q

what does micropipette aspiration measure?

A
  • Measures membrane tension by measuring the membrane potential (membrane clamping)
23
Q

what are optical tweezers?

A

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

24
Q

what do magnetic tweezers measure?

A
  • Measure the tensile strength or the force generated by molecules
25
Q

what do mechanosensors sense?

A

force

26
Q

3 mechanosensor examples?

A

Piezo channels
Integrins
Caveolae

27
Q

What are Piezo channels

A

Large ion channels (38 transmembrane domains)

28
Q

What are Piezo channels directly activated by

A

Mechanical activity

29
Q

There are the two ideas of how Piezo channels are activated. what is the first?

A
  1. When inserted into the plasma membrane, the channel will bend it. The application of a mechanical force to flatten the membrane will open the channel.
30
Q

There are the two ideas of how Piezo channels are activated. what is the second?

A
  1. The channel sits laterally within the membrane. There is no bending. The application of a mechanical force - either directly to the channel or through the actin cytoskeleton being pulled, will open the channel.
31
Q

How do we know actin plays a role in opening Piezo channels?

A

It has been shown that actin does play a role, as the loss of actin means that higher forces are needed to open the channel.

32
Q

Describe the mechanosensingroles of Piezo1 in organisms

A

• Sensing endothelial fluid flow;
- If there is no flow, cells are disordered
- With flow, cells are ordered, including their actin cytoskeleton
• Regulating smooth muscle tone (inc. vascular tone);
• Altering red blood cell membrane tension through volume regulation
• Sensing lung tissue stretch to regulate breathing;
• Proprioception.

33
Q

How do integrins work?

A

Integrins form dimers, and transduce conformational changes from the inside out (the opposite to usual when a ligand binds to a receptor), allowing interaction with the extracellular matrix.

34
Q

What can integrins cluster into?

A

Focal adhesion complexes

35
Q

What binds integrin to the actin cytoskeleton?

A

Talin - adaptor protein

36
Q

What sort of molecule is Talin? What is the implication of this?

A

Mechanosensitive molecule - Talin can change its structure depending on the force applied to it.

37
Q

What happens to Talin when a bigger force is applied?

A

It unfolds

38
Q

How does Talin interact with F-actin?

A

Talin elongates and binds to F-actin. This change in conformation opens out further adhesion sites, exposing binding sites, onto which vinculin can bind.

39
Q

When can Vinculin bind to Talin?

A

When talin is partially unfolded, otherwise the binding sites are occupied

40
Q

What is necessary for Vinculin to bind to talin

A

When a force is applied

41
Q

When do mature focal adhesions only form?

A

When force is applied

42
Q

What contributes to the stabilisation of the focal point?

A

Vinculin

43
Q

In summary, what does the maturation of focal adhesions depend upon?

A

Force application, unfolding of talin, binding of vinculin

44
Q

What is Talin replaced by? What does this form?

A

Tensin

Fibrillar adhesion complexes

45
Q

What are caveolae?

A

Stable membrane invaginations which are rich in Cavins 1-4, linked to the actin cytoskeleton/stress fibers via Cavin 1

46
Q

What happens when shear stress/increase in membrane tension?

A

Caveolae flatten, dissociating cavin complexes and initiating signal transduction

47
Q

Caveolae sense…

A

Stretch

Cell and molecular extras (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions