Introduction mechanobiology

Question 1

What is seen when bone mineral concentration (BMC) is compared to muscle mass?

Answer 1

That the larger the muscle mass is, the higher the BMC is.

Question 2

What cells are responsible for scar formation?

Answer 2

Myofibroblasts

Question 3

What is usually/can be a result of an ankle sprain on bones?

Answer 3

That there is cartilage damage.

Question 4

What is hydraulic stress?

Answer 4

The internal force per unit when the force is applied by the fluid on the body.

Question 5

Is hydraulic stress a feature of healthy or unhealthy cartilage?

Answer 5

Healthy cartilage

Question 6

What is cartilage mostly made out of?

Answer 6

Collagens, proteoglycans and water.

Question 7

What is deviatoric stress?

Answer 7

A stress component in a system which consists of unequal principal stress. Deviatoric stresses control the degree of body distortion.

Question 8

What is the difference between hydraulic and deviatoric stress?

Answer 8

• The biggest difference between the two is the fact that hydraulic stress is ‘just’ the force put on the body caused by fluid and that deviatoric stress refers to the unequal division of pressure in the body.
• Besides this, hydraulic stress causes the driving of fluid flow, while deviatoric stress causes deformation.

Question 9

What is the difference between anabolism and catabolism in regard to bones and specifically cartilage of bones?

Answer 9

• Anabolism is the building-up aspect of metabolism, while catabolism is the breaking-down aspect of metabolism.
• This also means that there are certain anabolic molecules (e.g. collagen 2, sox5/6/9, anti-inflammatory macrophages, etc.) that promote the production of cartilage and certain catabolic molecules (e.g. IL1, IL6, IL8, MMP, apoptosis) that inhibit/diminish the production of cartilage.

Question 10

What is the result of impact (i.e. increased force) on cartilage?

Answer 10

Impact destroys the collagens that confines proteoglycans and water.

Question 11

So what is the difference between healthy and impacted cartilage?

Answer 11

• Healthy cartilage has hydraulic stress (anabolic processes).
• Impacted cartilage has deviatoric/shear stress (catabolic and inflammatory processes)

Question 12

What is meant with the vicious circle of degeneration of impacted cartilage?

Answer 12

Biomechanics of the cell (e.g. hydraulic and deviatoric stress on the cell) influences the cell (structure/function/etc.) and the structure/function/etc. of the cell influences the extracellular matrix of the cell, which in its turn influences the biomechanics of the cell again.

Question 13

Stem cells are grown on a substrate and differenitated into nerve, muscle and bone cells.
What is the effect of stiffness on these cells?

Answer 13

Stiffness can regulate cell growth, by e.g. controlling apoptosis.

Question 14

Name factors that influence the cell volume and cell shape.

Answer 14

• Soft or stiff substrate (i.e. fat or bone cells).
• Cell density
• Island shape (on plate)
• Dynamic loading

Question 15

What three components make up the cytoskeleton?

Answer 15

• Microfilaments
• Microtubules
• Intermediate filaments

Question 16

Describe the characteristics of microfilaments.

Answer 16

• E.g. filopodia made up of protein actine.
• Important for tension and contraction.
• Intracellular motor transport (interaction with other proteins).

Question 17

Describe the characteristics of microtubules.

Answer 17

• Important for compression and transport.
• Round and hollow cylinders made out of tubulin.

Question 18

Describe the characteristics of intermediate filaments.

Answer 18

• Made out of fibrous proteins
• Organised to a strong, rope-like structured network that supports cell structure and stability.

Question 19

What is tensegrity?

Answer 19

• Tensegrity = integrity and tension
• Tension → causes integrity.

Question 20

What is mechanotransduction?

Answer 20

Mechanisms by which cells convert mechanical stimuli (e.g. tension, osmosis, compression, shear, fluid, topography) into electrochemical activity (ultimately influences cell function such as survival, apoptosis, proliferatoin and differentiation).

Question 21

What molecules are important for cell-matrix connection?

Answer 21

Integrins

Question 22

What function has the protein vinculin?

Answer 22

A protein that couples, transmits, transduces and regulates mechanical force between the cytoskeleton and adhesion receptors (e.g. integrins). For example, vinculin is able to link integrins with the contractile actin-myosin cytoskeleton.

Question 23

What is the function of:
- adherens
- desmosomes

Answer 23

• adherens → connects actin filament bundle in one cell with that in the next cell
• desmosomes → connects intermediate filaments in one cell to those in the net cell

Question 24

How are lamina able to influence the ECM?

Answer 24

There is communication to the nucleus through the lamina:
- low lamin A/lamin C (lamin A/C) ratio → soft ECM
- high lamin A/C ratio → stiff ECM

Question 25

What are caveoli and how do they influence cell volume?

Answer 25

- Caveoli are invaginations of the plasma membrane and with this, are vesicles that are able to absorb fluids. - Because caveoli are able to absorb fluids, caveoli consequently influence cell volume and size.

Question 26

How is extracellular fluid flow sensed?

Answer 26

- Membrane channel gating → the stretching of the membrane triggers channels to open, whereby molecules can flow in- and out of the cell. - Membrane fluidity and tension relief (property of the cell membrane that allows it to adapt its shape and movement to different conditions) - Cilia-dependent signaling - Glycocalyx and cytoskeleton torque - Cytoskeletal deformation