7.1 Cell adhesion and extracellular matrix

Cell adhesion molecules and the extracellular matrix are crucial for tissue formation and function. They enable cells to stick together, communicate, and interact with their surroundings. These components play vital roles in development, maintaining tissue structure, and regulating cell behavior.

Understanding cell adhesion and the extracellular matrix is key to grasping how tissues form and work. This knowledge helps explain developmental processes, tissue repair, and even disease progression. It's all about how cells connect and interact with their environment.

Cell Adhesion Molecules in Interactions

Types and Functions of Cell Adhesion Molecules

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• Cell adhesion molecules (CAMs) mediate attachment between cells or between cells and the extracellular matrix
• Four main families of CAMs exist with distinct characteristics
  • Cadherins facilitate calcium-dependent homophilic cell-cell adhesion (epithelial tissue formation)
  • Immunoglobulin superfamily CAMs enable homophilic and heterophilic interactions (neural development, immune responses)
  • Selectins mediate transient cell-cell adhesion (leukocyte trafficking during inflammation)
  • Integrins connect the cytoskeleton to the extracellular matrix (cell-matrix adhesion, bidirectional signaling)
• CAMs participate in mechanotransduction by converting mechanical stimuli into biochemical signals
  • Influence cell behavior and gene expression
  • Example: Stretch-activated ion channels in vascular endothelial cells

Roles in Cellular Processes

• Cadherins play crucial roles in tissue formation and maintenance
  • E-cadherin in epithelial cell adhesion
  • N-cadherin in neural tissue development
• Immunoglobulin superfamily CAMs contribute to diverse cellular processes
  • NCAM in neurite outgrowth and synaptic plasticity
  • ICAM-1 in leukocyte adhesion during immune responses
• Selectins facilitate leukocyte rolling and adhesion in blood vessels
  • E-selectin on endothelial cells
  • P-selectin on platelets and endothelial cells
  • L-selectin on leukocytes
• Integrins mediate cell-matrix adhesion and bidirectional signaling
  • α5β1 integrin binding to fibronectin
  • αvβ3 integrin in angiogenesis and bone resorption

Extracellular Matrix Composition and Functions

Structural Components and Their Roles

• Extracellular matrix (ECM) forms a complex network providing support to surrounding cells
• Major structural components include:
  • Collagens provide tensile strength (Type I collagen in skin and bone)
  • Elastin contributes to tissue elasticity (blood vessels, lungs)
  • Fibronectin offers cell attachment sites and organizes other ECM components
• Proteoglycans consist of a core protein with attached glycosaminoglycan chains
  • Contribute to hydration and compressive strength of ECM
  • Examples: Perlecan in basement membranes, aggrecan in cartilage
• Glycoproteins play crucial roles in basement membrane formation and cell-matrix interactions
  • Laminin supports epithelial cell adhesion and polarization
  • Nidogen links other ECM components

Functional Aspects of the Extracellular Matrix

• ECM serves as a reservoir for growth factors and cytokines
  • Regulates their availability and activity in the cellular microenvironment
  • Example: FGF binding to heparan sulfate proteoglycans
• Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) regulate ECM remodeling
  • Influence tissue homeostasis and morphogenesis
  • MMP-2 and MMP-9 in basement membrane degradation during cancer metastasis
• ECM composition and organization vary among different tissues
  • Reflects specific functional requirements and developmental origins
  • Bone ECM rich in collagen and hydroxyapatite for strength
  • Cartilage ECM abundant in proteoglycans for cushioning

Importance of Cell Adhesion and Extracellular Matrix in Tissue Organization

Developmental Processes and Tissue Architecture

• Cell adhesion and ECM establish and maintain tissue architecture
  • Provide physical support and biochemical cues for cells
• Differential cell adhesion drives cell sorting and tissue boundary formation
  • Example: Separation of germ layers during gastrulation
• ECM provides a scaffold for cell migration and tissue patterning
  • Guides morphogenetic movements during organogenesis and tissue repair
  • Neural crest cell migration along ECM pathways
• Interactions between cells and ECM regulate crucial processes in tissue organization
  • Cell polarity establishment (apical-basal polarity in epithelial cells)
  • Differentiation (ECM-induced differentiation of mammary epithelial cells)
  • Fate determination (ECM influence on stem cell lineage commitment)

Tissue Homeostasis and Disease Implications

• ECM composition and mechanical properties influence stem cell behavior
  • Play a key role in niche formation and maintenance
  • Example: Bone marrow niche for hematopoietic stem cells
• Dynamic remodeling of cell adhesions and ECM enables tissue morphogenesis
  • Allows for cell rearrangements and shape changes during development
  • Convergent extension movements in embryonic axis elongation
• Dysregulation of cell adhesion or ECM composition leads to various conditions
  • Developmental abnormalities (cleft palate due to defective cell adhesion)
  • Fibrosis (excessive ECM deposition in liver cirrhosis)
  • Cancer progression (altered cell-ECM interactions in metastasis)