Tissue mechanics, mechanotransductor and fibrosis Flashcards
what is the young’s modules?
a measure of stiffness/elasticity
in the young’s modules, what’s the least stiff tissue?
brain
in the young’s modules, what’s the most stiff tissue?
bone
what are the mechanical properties of tissues matched to?
function of tissues
what maintains a steady state of tissues?
homeostatic systems
what is mechanotransduction?
the conversion of mechanical input into a biochemical signal inside the cell
how can cells ‘feel’ stiffness?
by deforming their surroundings
what does mechanical regulation of transcription factors allow?
control of specific genetic programmes
what leads to fibrosis?
misregulation of feedback and loss of homeostasis- cells deposit too much EDM
what is tissue composed of?
tissues and ECM
are we more ECM or cells?
ECM
what’s the communication between ECM and cells like?
cells surrounded by ECM receive a signal from ECM (chemical or mechanical). then produce a response to change or maintain function
what is cell behaviour controlled by?
stiffness
how does stiffness alter cell morphology?
cell shape depends on the stiffness of the gel they are put on- adherent cells spread more on stiffer surfaces
how does stiffness affect cell contractility?
cells pull harder (are more contractile) on stiffer substrates
how does stiffness affect cell proliferation/growth?
it’s faster on stiffer surfaces
how does stiffness affect cell apoptosis?
less apoptosis in stiff substrates
how does stiffness affect cell movement/duotaxis?
cells migrate towards stiffer surfaces
how does stiffness affect cell differentiation?
soft substances drive differentiation to soft tissue types
stiff substances drive differentiation to stiff tissue types
how do cells respond to mechanical signals in terms of focal adhesion and cytoskeletal remodelling?
- 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
what do mechanosensitive ion channel down?
mechanical action causes ion channels to open
ions come in and change cell environment- signalling cascade
what’s continuous mechanical linkage to nucleus?
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
what’s translocation of transcription factors?
transcription factor YAP1 is nuclearly localized to drive osteogenic differentiation
what does fibrosis do?
makes cells stiffer so mechanical properties no longer match the tissue’s function
what’s the normal role of fibroblasts?
synthesising ECM
name 3 fibrotic diseases
- glaucoma
- heart attack
- atherosclerosis
- COPD (chronic obstructive pulmonary disease)
what happens if there’s too much scarring?
inhibits function
what’s idiopathic pulmonary fibrosis (IPF)?
- 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
