Surprise!
Where does MRFT localize on a stiff subsrate
Nuculus
What is tensile homeostasis
Cells must balance the external and internal forces in order to sense external stimuli and generate a proper response
Name 2 characteristics of the extracellular environment that disorders/ diseases could disturb
1. Applied force/deformations
2. ECM composition change
During blood clotting what does your body begin to create/recruit
ECM components - stiffer matrix
Activation of which transcriptional proteins are found in human tumors?
YAP/TAZ
Mesenchymal stem cells exhibit _____ (2 words)
Mechanical memory
What could disturb tensile homeostasis
a challenge (ie. disease)
Name 2 cell structure/organization characteristics that disorders/ diseases could disturb
1. Transmembrane proteins (integrins, ion channels)
2. Cytoskeletal force generation (actomyosin contraction)
3. Internal stress mechanosensory (YAP/TAZ, MRTF)
During wound healing, a stiffer matrix is initiated, what type of force is created?
Traction
Cancer-associated ______ are found in human tumors (major cell of connective tissue!)
fibroblasts
2 reasons you would first want to conduct an in vitro experiment
cheap, quick, ethical, easy, highly repeatable
Misregulation of tensional homeostasis has been proposed to drive ________ and promote progression of _______
disorganization of mechanical forces / imbalance of internal and external force
disease / pathological conditions
Name 2 nuclear / transcriptional characteristics that disorders/ diseases could disturb
1. LINC protein
2. Nuclear shape
3. Transcription activity (YAP/TAZ)
What growth factor increases at the site of a wound during healing
TGFbeta
Name a mechanotransduction hallmark of tumors. What type of feedback is this?
Stiffening, more cancer-associated fibroblasts and more nuclear YAP/TAZ
Positive feedback
Dysregulated wound healing and inflammation can lead to what pathological state
Fibrosis - can cause scarring
Chronic inflammation / very fibrotic environment. This can cause internal damage
Where do tumors move after they have progressed? What allows for its adherence and survival in this new environment
To the blood, YAP/TAZ (stiffness)
How could you reduce scarring on a wound in an experiment?
erase of memory of MSC or treat cells with soft primed MSC
In a very simple sense, name a potential mechanotherapuetic for tumors
Targetting tissue stiffness, ie. TGFB inhibitor, a focal adhesion kinase inhibitor, MMP inhibitor