MSE 536- SP2025_Biological Systems

MSE 536

• Course Title: Advanced Biomaterials

• Focus: Biological Systems

Cell-Surface Interaction

• Biomaterial surface properties: Affect protein attachment.

• Composition of adsorbed layer: Dictates cell attachment.

• Protein–cell interactions: Typically occur via receptor-ligand interactions.

• Cell-substrate interactions (biomaterial + adsorbed proteins): Influence various cell functions, including:

  1. Viability

  2. Communication

  3. Protein synthesis

  4. Proliferation

  5. Migration

  6. Activation/differentiation

  7. Programmed cell death

Cell Types

1. Differentiated Cells:

   • Perform tissue-specific functions and are specialized for specific jobs (e.g., osteoblasts for bone growth, chondrocytes for cartilage, endothelial and smooth muscle cells for vasculature).

2. Undifferentiated Cells (Progenitor Cells):

   • Can differentiate into various cell types and have not become specialized.

   • Differentiation: A controlled series of changes, typically involving changes in gene expression and protein synthesis.

Cellular Structure

• Key Cell Components:

  • Plasma membrane

  • Mitochondria

  • Golgi apparatus

  • Cytoplasm

  • Lysosomes

  • Cytoskeleton

  • Nucleus

  • Smooth endoplasmic reticulum

  • Rough endoplasmic reticulum

• Nucleus: Contains the nucleolus, where ribosomes are assembled.

Cell Components

• Cell Membrane:

  • Divides cell from external environment (cytoplasm).

  • Structure: Bi-layered of phospholipids with hydrophilic heads and hydrophobic tails.

  • Functions:

    • Protective barrier

    • Regulates transport (selectively permeable)

    • Allows cell recognition

    • Provides anchoring sites for cytoskeleton filaments

Cell Membrane Proteins

• Transmembrane Proteins:

  • Span the membrane with hydrophilic and hydrophobic domains.

  • Types:

    1. Channel Proteins: Form small pores for ion passage (e.g., Na+, K+, Ca2+, Cl-).

    2. Carrier Proteins: Physically bind and transport molecules against concentration gradient.

• Anchored Proteins:

  • Receptors projecting into extracellular space and intracellular space.

Cytoskeleton

• Definition: Protein-based structures that change in length and impart shape to the cell.

• Functions: Cell motility and movement.

• Elements:

  1. Actin microfilaments: 6-8 nm diameter

  2. Intermediate filaments: 10 nm diameter; attach to receptors translating external signals.

  3. Microtubules: 25 nm diameter; separate duplicated DNA before cell division.

Mitochondria

• Function: Energy production via oxidative phosphorylation.

• Structure: Two phospholipid membranes; inner membrane folded to surround matrix.

  • Matrix contains enzymes to break down molecules like glucose.

  • ATP Production: ATP formed is transported and hydrolyzed to ADP for energy use (e.g., ion pumping).

Nucleus

• Role: Control center of the cell.

• Contains: Genetic information as DNA condensed into chromatin.

• Nuclear Envelope: Two phospholipid membranes with nuclear pores for selective substance passage.

• Nucleolus: Ribosome assembly site.

DNA Structure

• Function: Contains thousands of information-rich genes.

• Gene Expression: When a gene is expressed, the corresponding protein is produced.

• Composition of DNA:

  1. Phosphate group

  2. Sugar

  3. Base

• Polymerization: Nucleic acids form a sugar backbone (deoxyribose).

DNA/RNA Bases

• Pyrimidines (Single-ring Structures): Thymine (T), Cytosine (C) in DNA; Uracil (U) replaces T in RNA.

• Purines (Double-ring Structures): Adenine (A), Guanine (G).

• Double helix structure: Approximately 10 base pairs per turn, stabilized by hydrophobic interactions.

DNA Structure

• 3D Structure: Double helix with sugar and phosphate backbone.

• Base Pairing: A with T, G with C through hydrogen bonds.

RNA Structure

• Differences from DNA:a. Single-stranded.b. Ribose sugar with an extra oxygen.c. Thymine replaced by Uracil.

• Function: Participates in DNA synthesis and protein production.

RNA Types

1. Messenger RNA (mRNA): Synthesized during transcription of genes; complementary to DNA.

2. Transfer RNA (tRNA): Adaptor molecule for mRNA translation; helps form ribosomes.

3. Ribosomal RNA (rRNA): Central to ribosomes; decodes mRNA into amino acids, interacts with tRNA during translation.

Endoplasmic Reticulum (ER)

• Structure: Long flattened sheets of phospholipid membranes.

• Functions: Protein synthesis.

  • Rough ER: Ribosomes present; catalyze protein synthesis.

  • Smooth ER: Tubular, lacks ribosomes.

Golgi Apparatus

• Role: Processes proteins after ER packaging.

• Functions: Modifies, sorts, and packages proteins for their final destinations (to organelles or extracellular release).

Vesicles

• Function: Transport between ER and Golgi or to target destinations.

• Exocytosis Process: Release proteins via vesicle fusion with the cell membrane.

• Endocytosis Process: Ingest external particles through specialized vesicles.

  • Incorporation with lysosomes aids breakdown of ingested materials.

Membrane Receptors

• Outside-in signaling: Cell functions altered by extracellular interactions.

• Inside-out signaling: Cell modifies its environment through secretion/rearrangement of contacts.

• Role of Receptors: Protein-based receptors like integrins enable these processes.

Cell-Cell Contacts

1. Tight Junctions: Prevent passage between cells.

2. Gap Junctions: Hydrophilic channels connecting membranes.

3. Desmosomes: Mechanical attachments involving cadherin receptors.

• Types: Belt (broad band) and Spot (specific spots).

Cell-ECM Contacts

• ECM: Extracellular matrix.

• Integrins: Receptors mediating strong adhesion to ECM.

• Common Contacts:

  1. Hemidesmosomes: Connect epithelial cells to basement membrane.

  2. Focal Adhesions: Connect cells to ECM, aiding migration and signaling.

Membrane Receptors and Ligands

• Receptors: Specific to ligands, crucial for cellular interactions.

• Types of Receptors:

  1. Cadherins: Form desmosomes through calcium-dependent binding.

  2. Selectins: Participate in cell binding through carbohydrate interactions.

  3. Mucins: Protein-based molecules presenting ligands for selectin binding.

  4. Integrins: Transmembrane proteins for cell–cell and cell–matrix contacts, linked to intermediate filaments.

  5. CAMs: Mediate interactions via heterophilic and homophilic binding.

Extracellular Environment

• Importance: Understanding cell-ECM interactions is essential for biomaterial design.

• Dynamic Contacts: ECM interactions influence cell shape/function during biomaterial implantation.

  • ECM structure as fiber-reinforced composites with collagen and elastin.

Collagen

• Abundance: Most prevalent protein in mammals, responsible for tissue tensile strength.

• Types: Common fibrillar collagens (Types I, II, and III).

• Structure: Triple helix of polypeptide chains (glycine-X-Y pattern).

Amino Acid Residues of Proteins

• Chart of Amino Acids: Includes one-letter and three-letter symbols, molecular weights, and pK values.

• Examples: Alanine (Ala, A), Glutamate (Glu, E), Leucine (Leu, L).

Assembly of Collagen Fibers

• Process:

  1. Procollagen secretion into extracellular space.

  2. Cleavage of peptide sequences.

  3. Fibril packing and fiber assembly with increased crosslinking for improved mechanical properties in applications.

Elastin

• Function: Forms elastic fibers for resiliency and extensibility in ECM.

• Composition: 85% hydrophobic amino acids.

• Structure: Complex 3D network through lysine crosslinking.

Proteoglycans

• Interactivity: Extensive water interactions due to negative charge, forming hydrated chains.

• Components: Glycosaminoglycans (GAGs) and core proteins.

• Example: Aggrecan found in cartilage; Heparan sulfate has anticoagulant properties.

Glycoproteins

• Role: Links various tissue components.

• Examples:

  • Fibronectin: Binds to integrin receptors for focal adhesion formation.

  • Laminin: Cross-linked structure with integrin binding sites.

Other ECM Components

• Mineral Crystals: Calcium and phosphate ions in bone/teeth enhance modulus.

• Significance in Tissue Function: ECM proteins sequester growth factors for cellular function stimulation, affecting matrix remodeling.

Matrix Remodeling

• Process: Continuous remodeling of ECM with degradation and synthesis of new molecules.

• Role of Enzymes: Catalyze reactions for matrix remodeling and maintain cellular function.

ECM Molecules As Biomaterials

• Use: ECM molecules like collagen and proteoglycans serve as biomaterials.

• Challenges: Unwanted immune responses; Decellularization to lower rejection risk in grafts and replacements.