Extracellular Matrix & Pulmonary Fibrosis

pulmonary fibrosis

scarring of lungs that increase overtime until they can no longer provide enough oxygen to body’s tissues/organs

extracellular matrix

hydrogel created and adhered to by cells

hydrogen

crosslinked polymer gel filled with aqueous solution

structural fiber components

collagen and elastin

hydrated matrix is composed of

extracellular fluid and proteoglycans (pgs)

adhesion molecules

mediate interactions between ECM and cell, receptors serve structural role

elastin as an entropic spring

stretching a polymer increases its order, making entropy negative and making G more positive and unfavorable, system naturally favors state of higher entropy (lower order and more randomized conformation)

extracellular (interstitial) fluid

what cells live in and like, nearly isotonic with cytoplasm, low in protein, sodium and chloride are major ions, ex. IV fluid

Ringer’s Lactate

Provides sodium, calcium, chloride, and bicarbonate in concentrations that mimic physiological extracellular fluid levels

saline

0.9% NaCl

IV fluid

made up of saline and Ringer’s Lactate

basal lamina (basement membrane)

specialized sheet of ECM under epithelial and endothelial cell layers, provides structural support, is transport barrier, phenotypic regulation; composed of collagen type IV, laminin, nidogen, perlecan, fibroectin

connective tissue/interstitium

collection of proteins and carbohydrates produced by cells that forms a matrix outside cell

sodium bicarbonate

perfect buffer

cell culture

composed of Dulbecco’s Modified Eagle’s Medium (DMEM), ions, amino acids, glucose, bicarbonate buffer, phenol red (pH indicator); supplemented with things like calf serum to provide growth factors and cytokines

collagen type IV

primarily found in basal lamina, more interruptions in helical structure = more flexible, provides tensile strength to basal lamina, accounts for 50% of basal lamina protein

laminin

bridging molecule for attaching cells to matrix components, found exclusively in basal lamina, binding site for cell surface receptors, deparin/heparan sulfate, type IV collagen, nidogen/entactin

nidogen/entactin

glycoprotein that bridges laminin and collagen IV in basal lamina

perlecan

heparan sulfate proteoglycan, bridges laminin and collagen IV in basal lamina

fibronectin

binds cells to matrix and guides cell movement, can be soluble/insoluble, contains binding sites for cell surface receptors and extracellular components (heparin, fibrin, collagen), found everywhere

integrins

heterodimeric proteins that have alpha and beta subunit, specific subunits determine ligand specificity, RGD is common sequence in ligands

focal adhesions

signaling platform for cells triggered by clustering of integrins, normal cells don’t grow unless they are adherent/stuck to their environment (cancer cells los this requirement)

cell adhesion molecule (CAM)

cell-cell adhesion receptor, homophilic association, N-CAM = neural cell adhesion molecule

cadherins

homophilic associated, calcium-dependent, E-cadherin = epithelial cadherin

lectin

bind oligosaccharides on glycoproteins

integrins

can bind cells to cells (heterophilic association) as well as cells to the matrix

fibroblasts

predominant cell type in connective tissues, secrete abundant amounts of ECM molecules

myofibroblast

state of activated fibroblasts by injury or inflammation for increased ECM deposition, secrete more ECM proteins (collagen)