Cell Adhesion 2 new

what is the extracellular matrix?

a complex network of macromolecules secreted by cells that provide structural and biochemical support to surrounding cells

what are the major classes of ECM macromolecules?

fibrous proteins (collagens, elastins), adhesive glycoproteins (fibronectin,laminin) and proteoglycans

how do cells interact with the ECM?

by cell surface adhesion receptors such as integrins

what are the main functions of the ECM

to provide tructural support, segregate tissues, influence cell survival , prolliferation, migration and differentiation

how does the ECM composition vary?

it differs according to tissue type and functional requirements

what is the basal lamina?

a thin, specialised sheet of EXM that underlies epithelial and endothelial cells

what are the main functions of the basal lamina?

structural support, filtration, tissue compartmentalization and regulation of cell behaviour

what are the main components of the basal lamina?

laminin, type 4 collagen, nidogen and perlecan (proteoglycan)

what is laminin ?

a key glycoprotein that forms a web like network and binds to integrins and other ECM molecules

what is the role of type 4 collagen in the basal lamina?

to provide tensile strength and form a supportive scaffolding with laminin

what is nidogen?

a linking protein that connects laminin and type 4 collagen networks

what are integrins?

heterodimeric transmembrane receptors composed of alpha and beta subunits that mediate cell-ECM adhesion

how do integrins connect inside the cell?

the ECM outside to the actin or intermediate filament cytoskeleton inside the cell

what are the 2 main types of integrin mediated adhesions?

focal adhesions and hemidesmosomes

what do focal adhesions connect to?

the actin cytoskeleton

what do hemidesmosomes connect to?

intermediate filaments, via intrgrin laminin keratin linkages

how does integrin activation affect cell behaviour?

promotes adhesion, spreading, migration and can prevent apoptosis

what are focal adhesions?

dynamic, integrin rich sites where the cell attaches to the ECM and connects to actin filaments

how can focal adhesions be visualized experimentally?

using fluorescently tagged actin or integrin binding proteins

what are hemidesmosomes?

specialised junctions anchoring epithelial cells to the basal laminate via integrins

which cytoskeletal element is linked by hemidesmosomes?

intermediate filaments - keratin

which basal laminate protein binds to hemidesmosomal integrins?

laminin

what is the function of hemidesmosomes?

provide strong, stable adhesion between epithelial cells and the underlying matrix

what are proteoglycans?

ECM components consisting of a core protein covalently linked to glycosaminoglycan (GAG) chains 

what are GAGs?

long, unbranched polysaccharides made of repeating disaccharide units

what are the properties of GAGs?

highly negatively charged, attracts water and cations, forming hydrated gels that resist compression

what is the role of proteoglycans in the ECM?

they provide hydration, resist compressive forces, and regulate diffusion of signalling molecules

what is hyaluronic acid?

a large, non-sulfated GAG that forms hydrated matrices and lubricates joints

how do proteoglycans influence signalling?

they bind and modulate growth factor availability and activity

what is fibronectin?

a glycoprotein in the ECM that connects cells to collagen fibres via integrins

what is the function of fibronectin fibrils?

form a network that guides cell movement and supports tissue structure

which enzymes degrade ECM components?

matrixmetalloproteinases (TIMPs)

why is ECM remodelling important in development and disease?

it allows cell migration and tissue remodelling but excessive degradation contributes to cancer invasion and metastasis

how can abnormal ECM cause disease?

mutations in ECM components or their receptors can lead to tissue fragility, fibrosis or impaired healing

how do cancer cells use ECM remodelling?

they secrete MMPs to degrade the surrounding matrix which facilitates invasion and metastasis

what role does the ECM play in wound healing?

it provides a provisional scaffold (via fibronectin and fibrin) for cell migration and tissue repair

what happens to ECM composition during tissue repair?

temporary ECM is replaced by collagen rich mature ECM

what is fibrosis?

the excessive accumulation of ECM components leading to tissue stiffness and dysfunction