麻省理工大学：《生物材料——组织交互作用》教学讲义（英文版）B Structure and function of naturally occurring ECMs

2.79J/3.96JBEH441JHST522J Biomaterials-Tissue Interactions Outline of three lectures on ECMs A Irreversible healing of ECMs in different organs B Structure and function of naturally occurring ECMs C Synthesis of biologically active ECM models

2.79J/3.96J/BEH.441J/HST522J Biomaterials-Tissue Interactions Outline of three lectures on ECM s A. Irreversible healing of ECMs in different organs. B. Structure and function of naturally occurring ECMs. C. Synthesis of biologically active ECM models. 1

B Structure and function of naturally occurring ECMs

B. Structure and function of naturally occurring ECMs 2

a biologically active model of ECM acts as an insoluble regulator of cell function image removed due to copyright considerations

A biologically active model of ECM acts as an insoluble regulator of cell function image removed due to copyri image removed due to copyright consi ght considderati erations ons 3

Definition of unit cell process Soluble Regulator A Insoluble Product Soluble Cell Regulate Regulator B Control volume dv Unit cell process confined conceptually in a control volume d

Definition of unit cell process 4 Cell + Insoluble Regulator Product Soluble Regulator A Soluble Regulator B Control volume dV Unit cell process confined conceptually in a control volume dV

The Extracellular Matrices(ECMS Part I (summary of structure and function) Insoluble macromolecular networks Structure varies with organ; but different ECMs comprise few types of macromolecules(mostly collagen, elastin, proteoglycans )plus water(65%) ECM does not migrate, proliferate, synthesize proteins or contain DNA! Give and take of signals with cells. Ligands on ECM surface interact specifically with cell receptors (integrins) Partly determine the state of differentiation of cells

The Extracellular Matrices (ECMs) Part I. (summary of structure and function) 5 ƒ Insoluble macromolecular networks. ƒ Structure varies with organ; but different ECMs comprise few types of macromolecules (mostly collagen, elastin, proteoglycans) plus water (65%). ƒ ECM does not migrate, proliferate, synthesize proteins or contain DNA! ƒ Give and take of signals with cells. Ligands on ECM surface interact specifically with cell receptors (integrins). ƒ Partly determine the state of differentiation of cells

The extracellular matrices. Part (summary of structure and function Possibly play role of memory storage device which is used to record events(e.g, a recent cell migration), thereby informing cells of what has already been done and acting as"arrow in a kinetic process Often bind cytokines and growth factors and act as reservoirs of such molecules Loss of cell-matrix contact characterizes tumor cells just prior to spreading of cancer from one organ to another(metastasis) Determines the shape of animals and maintains positional homeostasis of organs. Recently, certain synthetic ECM models have induced organ regeneration in adults

The Extracellular Matrices. Part II. (summary of structure and function) 6 ƒ Possibly play role of memory storage device which is used to record events (e.g., a recent cell migration), thereby informing cells of what has already been done and acting as “arrow” in a kinetic process. ƒ Often bind cytokines and growth factors and act as reservoirs of such molecules. ƒ Loss of cell-matrix contact characterizes tumor cells just prior to spreading of cancer from one organ to another (metastasis). ƒ Determines the shape of animals and maintains positional homeostasis of organs. ƒ Recently, certain synthetic ECM models have induced organ regeneration in adults

The major ecM molecules 1. Collagens 2. Elastin 3. Proteoglycans and glycosaminoglycans(GAGs) 4. Cell-adhesion molecules(fibronectin, laminin others) 5. Water(about 65%)

The major ECM molecules 1. Collagens. 2. Elastin. 3. Proteoglycans and glycosaminoglycans (GAGs). 4. Cell-adhesion molecules (fibronectin, laminin, others). 5. Water (about 65%). 7

Schematic view of Ecm GAGs CS KS PG Collagen fiber

8 Schematic view of ECM ∆ιαγραµµατικη οψη EKM

Hierarchy of structural order in roteins Primary structure the complete sequence of amino acids(aa)in the polypeptide chain. scale: 1 nm Secondary structure: the local chain configuration sequence of 3-5 AA) Scale 10 nm Tertiary structure: the configuration of the entire macromolecule, scale: 100 nm

Hierarchy of structural order in proteins Primary structure: the complete sequence of amino acids (AA) in the polypeptide chain. Scale: 1 nm. Secondary structure: the local chain configuration (sequence of 3 - 5 AA). Scale: 10 nm. Tertiary structure: the configuration of the entire macromolecule. Scale: 100 nm. 9

Hierarchy of structural order in proteins(cont Quaternary structure: The packing pattern of several identical molecules that characterizes a crystalline fiber Scale: 1000 nm= 1 um Architecture: Pattern comprising several fibers of a protein that constitute a macroscopic tissue. Often contains fibers of two different proteins (collagen and elastin) and one or more proteoglycan molecules Scale: 1-10 mm

Hierarchy of structural order in proteins (cont.) Quaternary structure: The packing pattern of several identical molecules that characterizes a crystalline fiber. Scale: 1000 nm = 1 µm. Architecture: Pattern comprising several fibers of a protein that constitute a macroscopic tissue. Often contains fibers of two different proteins (collagen and elastin) and one or more proteoglycan molecules. Scale: 1-10 mm. 10