Cell Biology of Manual Therapies (Heck) Flashcards
Fascia
Connective tissue
Superficial fascia
Subcutaneous tissue
close to skin
Deep Fascia
more dense in structure
associated with muscle, bone, neurovascular tissues
no fat
Retinaculum
Associated with tendons
holds tendons in place when crossing a joint
Subserous
Lines the body cavities
allows tissues to slip and slide against one another
Bursae
Closed sacs of serous membrane capable of secreting fluid for lubrication
Cells of fascia (4)
Fibroblast
Macrophage
Mast Cell
Plasma cell
Fibroblast
responsive to mechantrasnduction
secrete the components of extracellular matrix
(glycoproteins, precursors of collagen, elastin)
Macrophage
Degrade/turnover ECM
secrete cytokines
inflammatory mediators
Mast Cell
Vasoactive
recruits cells to location
associated with capillaries
Plasma Cell
Produce antibodies
under normal conditions these are in low conc.
Extracellular matrix of fascia
Collagens (most abundant)
Glycoproteins
Proteoglycans
Transmembrane proteins interacting with ECM
Fascia Connective tissue types
Loose (areolar) CT
Dense Regular Connective
Dense Irregular Connective
Depending on type of CT, fibroblasts response and ability to response is different
Fascia Connective tissue types
Loose (areolar) CT
Dense Regular Connective
Dense Irregular Connective
Depending on type of CT, fibroblasts response and ability to response is different
The Fibroblast
CT type of cell
Least specialized in the CT family
Interconvertable
Can penetrate matrix and become entangled within it
remodel matrices- goal to achieve tensional homeostasis
Interconvertable nature of fibroblasts
can differentiate into any of the CT cell types (cartilage, bone, adipose, smooth muscle)
Cell-Matrix Tension state
Dependent upon collagen density, matrix restraint, and growth factors
High cell-matrix tension (wound)
Activated fibroblast- make more ECM
Cell proliferation ON
Matrix Biosynthesis ON
Restrained Collagen Matrix
4 dimensions of cellular mechanics
Low tension / Pro-Migratory
High Tension / Pro-Migratory
Low Tension / Pro-contractile
High Tension /Pro-contractile
Global matrix remodeling/contraction
The idea that a fibroblast can respond to mechanical stimulation and remodel the entire tissue
What happens during global matrix contraction in low tension state
collagen density increases within hours due to PDGF
characteristic fibroblast ruffles
High tension state (global matrix contraction)
ECM attached to surface and environment is not compressive
therefore cell can transfer energy to external clutch does not need microtubules for support
When can fibroblasts migrate
In low tension state
can’t be contracted because it needs its dendritic extensions to move
Myofibroblast
Differentiated fibroblast
Adapt contractility activity to level of stress in the surrounding
Highly Contractile Myofibroblast
Stress fiber formation
Expression of alpha-smooth muscle actin
Alpha smooth muscle actin
Mechanosensitive protein
Expressed under significant mechanical load
Myofibroblast normal physiology
Cell contraction–> participates in wound healing
releases factors located in ECM (such as TGF-beta)
TGF beta release
stimulated by mechanical movement of cell
Happens when we have contractile cell and stiff high tension matrix that resists contraction of cell
Myofibroblast in pathology
Organ fibrosis- release of TGF beta
Dupuytren’s Contracture- contracture of hand
Dupuytren’s Contracture
contraction of palmar aponeurosis
PDGF
Procontractile and pro-migratory in low tension
Anitcontractilie in high tension
TGF-Beta
Myofibroblast differentiation
lie latent in ECM pools until released by contracilie mechanisms or proteolytic cleavage
Focal adhesions
link ECM with actin cytoskeleton
contains integrin
allows for downstream signaling transduction to occur
mechanical –> kinase cascade (for example)
Integrin
transmembrane protein
ligand binding causes integrin to cluster and recruit many proteins to the cytosolic domain that then create a mature focal adhesion
Methods of mechanical cell stimulation
Compression
Static stimuli (tissue stiffness)
Stretch
Uniaxial (one direction)
Biaxial
Equibiaxially
Normal function of fibroblasts
Secrete ECM
Wound healing
State that fibroblasts exist in normally
Low Tension
Includes: Dendritic morphology
Network through gap junctions
low matrix biosynthesis
What happens during global matrix contraction in high tension state
Collagen density increases within hours due to extracellular environment
Tensegrity
Tensional integrity
unison of tensioned and compressed parts
Low tension state (floating matrix) (global matrix contraction)
cells forming dendritic extensions (microtubles and actin)
loose floating matrix is more compressive on cell, therefore cell uses its own cytoskeletal elements to act as a clutch
Cell signaling involved in mechanotransduction
PDGF
LPA
S1P
TGF-beta
LPA
Lysophosphatidic acid
induces proliferation
procontractile (of fibroblasts) in high tension
S1P
Procontractile in high tension environment
activated by GF and cytokines
induces proliferation and inflammation- stimulates wound healing
phospholipid- so paracrine signalling
Shear forces
Fluid flow
such as cells lining fluid-filled cavities and vessels
interstitial flow- generated via compression or inflammation
How do cells respond to uniaxial stretch
align along the perpendicular axis of the stretch
How do cells respond to biaxial stretch
Multiple directions
Subcellular stimulation
Comes from within the cell
Myosin V contraction
Can transduce signals from the cytoskeleton to the focal adhesions to the ECM
