Tissue mechanics, mechanotransductor and fibrosis

Question 1

what is the young’s modules?

Answer 1

a measure of stiffness/elasticity

Question 2

in the young’s modules, what’s the least stiff tissue?

Answer 2

brain

Question 3

in the young’s modules, what’s the most stiff tissue?

Answer 3

bone

Question 4

what are the mechanical properties of tissues matched to?

Answer 4

function of tissues

Question 5

what maintains a steady state of tissues?

Answer 5

homeostatic systems

Question 6

what is mechanotransduction?

Answer 6

the conversion of mechanical input into a biochemical signal inside the cell

Question 7

how can cells ‘feel’ stiffness?

Answer 7

by deforming their surroundings

Question 8

what does mechanical regulation of transcription factors allow?

Answer 8

control of specific genetic programmes

Question 9

what leads to fibrosis?

Answer 9

misregulation of feedback and loss of homeostasis- cells deposit too much EDM

Question 10

what is tissue composed of?

Answer 10

tissues and ECM

Question 11

are we more ECM or cells?

Answer 11

ECM

Question 12

what’s the communication between ECM and cells like?

Answer 12

cells surrounded by ECM receive a signal from ECM (chemical or mechanical). then produce a response to change or maintain function

Question 13

what is cell behaviour controlled by?

Answer 13

stiffness

Question 14

how does stiffness alter cell morphology?

Answer 14

cell shape depends on the stiffness of the gel they are put on- adherent cells spread more on stiffer surfaces

Question 15

how does stiffness affect cell contractility?

Answer 15

cells pull harder (are more contractile) on stiffer substrates

Question 16

how does stiffness affect cell proliferation/growth?

Answer 16

it’s faster on stiffer surfaces

Question 17

how does stiffness affect cell apoptosis?

Answer 17

less apoptosis in stiff substrates

Question 18

how does stiffness affect cell movement/duotaxis?

Answer 18

cells migrate towards stiffer surfaces

Question 19

how does stiffness affect cell differentiation?

Answer 19

soft substances drive differentiation to soft tissue types

stiff substances drive differentiation to stiff tissue types

Question 20

how do cells respond to mechanical signals in terms of focal adhesion and cytoskeletal remodelling?

Answer 20

• cell relationship with cytoskeleton uses actin, myosin and integrins
• cells pull on their surroundings (actin polymerises on edge of cell, pulled by myosin)
• if substrate is stiff, signalling proteins are activated (MAPK and RhoA) which turns on myosin and actin production to increase contractility of the cell so it pulls harder on stiff substrate

Question 21

what do mechanosensitive ion channel down?

Answer 21

mechanical action causes ion channels to open

ions come in and change cell environment- signalling cascade

Question 22

what’s continuous mechanical linkage to nucleus?

Answer 22

as you apply force outside the cell, it’s transmitted through the ECM using focal adhesion, through cytoskeleton to nucleus. changes chromatin in nucleus to affect gene expression

Question 23

what’s translocation of transcription factors?

Answer 23

transcription factor YAP1 is nuclearly localized to drive osteogenic differentiation

Question 24

what does fibrosis do?

Answer 24

makes cells stiffer so mechanical properties no longer match the tissue’s function

Question 25

what’s the normal role of fibroblasts?

Answer 25

synthesising ECM

Question 26

name 3 fibrotic diseases

Answer 26

• glaucoma
• heart attack
• atherosclerosis
• COPD (chronic obstructive pulmonary disease)

Question 27

what happens if there’s too much scarring?

Answer 27

inhibits function

Question 28

what’s idiopathic pulmonary fibrosis (IPF)?

Answer 28

• dense ECM blocking area around air sacs in lungs- reduces gas exchange
• scar tissue drives into healthy tissue by myofibroblast core expansion
• builds up into mass of irregular matrix
• rare
• more in men
• idiopathic- unknown cause
• incurable
• 50% die in 2-3 years
• no repair from scar tissue