Introduction to Cell Communities

  • The course is titled "Molecular Biology of Cells II".
  • Instructor: Dr. Gregory Cole
  • Office: MTSB 2206, Email: gcole@nccu.edu

Overview of Tissues and Organs

  • Main focus on how cells are organized into tissues and organs in multicellular organisms.
  • Key aspects to explore include:
    • Mechanisms of tissue assembly.
    • Role of the extracellular environment in tissue organization.
    • Organization of various cell types into tissues.
    • Importance of the cytoskeletal network in tissue organization.

Extracellular Matrix (ECM) and Cell Junctions

  • ECM contributes to the structural integrity of tissues.
  • Various types of cell junctions will be examined for their roles in tissue stability.
  • Stem cells play a pivotal role in the renewal and repair of tissues.
  • Disorders of tissue renewal, especially related to cancer, will also be discussed.

Cell Strengthening in Tissues

Plant Tissues

  • Plant cells and tissues are fortified by cell walls.
    • Cellulose (blue) and pectin (green) are main components of plant cell walls, contributing to their support and strength.

Animal Tissues

  • Animal tissues rely on the extracellular matrix (ECM) and the cytoskeleton for structural strength.
  • Distinction between types of tissues:
    • Connective tissue: Composed mostly of ECM, varies widely in structure and strength (bone, skin, cartilage).
    • Other tissues (epithelial, muscle, nervous): Composed primarily of cells with lesser ECM.
    • Function of connective tissue is to bear mechanical stress (tension/compression).

Collagen in Connective Tissues

Importance of Collagen

  • Major fibrous proteins of the ECM, secreted in large quantities.
  • Collagen constitutes approximately 25% of total protein mass in mammals.
  • Characterized by a rigid triple-helix structure; rich in glycine and proline.
  • Structure defined by Gly-X-Y repeating units in collagen α-chain.

Formation of Collagen Fibrils

  • Mature collagen is produced from procollagen synthesized in the rough endoplasmic reticulum (rER).
  • Procollagen transported to Golgi apparatus and further processed before secretion.

Clinical Relevance

  • Defects in procollagen processing can result in diseases with weaker connective tissues.

Types of Collagen Structures

  • Varied structural networks formed by collagen in different connective tissues:
    • Skin shows opposing collagen bundle orientations (90° angles).
    • Tendons feature parallel bundles of collagen.
    • Some tissues have a meshwork of collagen fibers.

Cell-ECM Interactions

Mechanisms of Interaction

  • Cells interact with the ECM primarily through attachment or migration.
  • Surface receptors facilitate attachment, commonly using fibronectin, which binds to cell integrins.
    • Integrins are transmembrane receptors linking ECM to the actin cytoskeleton.
  • Importance of fibronectin in development; fibronectin null mutants often die early.

Basal Lamina

  • A specific form of ECM, important for cell attachment in epithelial tissues.
  • Epithelial cell's basal surface attaches to the basal lamina via integrins binding to laminin, a protein trimer.

Clinical Relevance of Integrins

  • Mutations in integrins can lead to deadly diseases, with specific consequences detailed in Table 19-4.
  • Overview of different integrins, ligands, their distributions, and clinical phenotypes when subunits are mutated.

Proteoglycans and Glycosaminoglycans in ECM

Composition and Functionality

  • Beyond collagen, proteoglycans and glycosaminoglycans (GAGs) are vital for the ECM.
  • These components provide space and binding sites for water and resist compression.
  • Density of connective tissue correlates with the amount of GAGs present.

Clinical Implications of GAGs

  • GAGs and proteoglycans important in cancer resistance mechanisms.
  • Example illustrating how changes in matrix components can link to aging and cellular pathways.

Epithelial Cells and Junctions

Organization of Epithelial Tissues

  • Epithelial tissues comprise multicellular sheets with defined polarity and specific functions (e.g., absorption, barriers).
  • Epithelial thickness varies: simple (one layer) and stratified (multiple layers).

Cell Junction Functions

  • Epithelial junctions fall into categories based on their role:
    • Occluding junctions: also known as tight junctions that seal cells together to prevent leakage.
    • Anchoring junctions: provide mechanical linkage among cells and to the ECM.
    • Channel-forming and signal-relaying junctions also present.

Role of Tight Junctions

  • Tight junctions prevent the diffusion of proteins, crucial for epithelial polarity and function.
  • Formed by proteins, including claudins and occludins, that maintain barrier integrity.

Cytoskeletal-Linking Junctions

  • Epithelial junctions are reinforced by cytoskeletal networks:
    • Adherens junctions and desmosomes provide anchorage using different cytoskeletal filaments.

Cadherins in Junctions

  • Classical cadherins vary between adherens junctions (actin-linked) and desmosomes (keratin-linked), contributing to tissue mechanical stability.

Hemidesmosomes

  • Connect epithelial cells to ECM via integrins, crucial for maintaining attachment.
  • Clinical relevance highlighted in the context of blistering diseases.

Gap Junctions

  • Allow passage of small molecules and ions between cells (less than 1000 daltons) using connexins.
  • Important for cell communication in tissues.

Tissue Maintenance and Renewal

Tissue Structure and Integrity

  • Tissues are heterogeneous mixtures of various cell types.
  • Require mechanisms for mechanical integrity, communication, and selective adhesion.

Cell Renewal Mechanisms

  • Tissues released from control can develop diseases like cancer related to loss of regulated cell renewal.
  • Stem cells play a fundamental role in the renewal process, generating differentiated cell types.

Classes of Stem Cells

  • Stem cells are self-renewing and can give rise to specialized progenitor cells (e.g., gut epithelium, hematopoietic lineage).

Clinical Application of Stem Cells

Embryonic Stem Cells

  • Pluripotent, able to differentiate into various cell types for therapeutic use, including transplant medicine.

Therapeutic and Reproductive Cloning

  • Somatic cell nuclear transfer can generate patient-specific embryonic stem cells applicable in regenerative medicine.

Induced Pluripotent Stem (iPS) Cells

  • Adult somatic cells can be reprogrammed to behave like embryonic stem cells without destruction of embryos, creating treatment avenues for several diseases.

Cancer as a Disease of Tissue Renewal

Disruption in Renewal Processes

  • Cancer arises when cellular renewal processes are disrupted by mutations, leading to unregulated growth.

Genetic Basis of Cancer

  • Mutations in oncogenes and tumor suppressor genes primarily responsible for cancer development.

Accumulation of Mutations

  • Cancer typically involves multiple mutations affecting key processes such as DNA repair, cell proliferation, and apoptosis.

Evolution of Cancer Cells

  • Mutations can provide competitive growth advantages and lead to further tumor development or metastasis.

Key Genes Involved in Cancer

  • Oncogenes (gain-of-function) promote cancer, while tumor suppressor genes (loss-of-function) prevent it.
  • Examples: Ras (oncogene), APC (tumor suppressor), and p53 (tumor suppressor).

Cell Signaling Pathways in Cancer

  • Understanding critical pathways (proliferation, survival, repair) is vital for determining potential targets for therapies.

Colorectal Cancer Example

  • Studied for association with APC mutations and subsequent polyp formation.

Advances in Cancer Treatment

Targeting Cancer Mechanisms

  • Strategies include immunotherapy, gene therapy, and oncolytic viruses to specifically target and destroy cancer cells.

Challenges in Treatment

  • Cancer cells evolve, complicating treatment protocols, and necessitating personalized approaches.

Future Directions

  • Cutting-edge treatments involve genome editing technologies, highlighting the ongoing evolution of cancer therapy and the potential for personalized medicine in treating genetic conditions.

Summary

  • This comprehensive examination outlines critical aspects of cell community organization, tissue maintenance, themes of cancer biology, and approaches to therapy. Topics covered include ECM dynamics, junction types, stem cell relevance, and the molecular basis of cancer.