Cellular and Molecular Bioengineering

Cellular and Molecular Bioengineering is a specialized field that applies quantitative engineering principles to understand, manipulate, and control biological processes at the cellular and molecular levels. It integrates concepts from molecular biology, biophysics, and chemical engineering to design and develop novel solutions for medical challenges. Key applications include creating advanced therapeutics like gene and cell therapies, engineering functional tissues and organs, developing sensitive diagnostic biosensors, and designing synthetic biological systems for targeted drug delivery and disease modeling.

1. Foundations of Cellular and Molecular Bioengineering
   1. The Cell as a System
      1. Eukaryotic Cell Structure and Function
         1. The Nucleus and Genetic Material
            1. Nuclear Envelope Structure
               1. Nuclear Membrane Composition
               2. Nuclear Lamina Organization
               3. Nuclear Envelope Dynamics
            2. Chromatin Organization
               1. Histone Proteins and Nucleosome Structure
               2. Chromatin Remodeling Complexes
               3. Heterochromatin and Euchromatin
               4. Epigenetic Modifications
            3. Nucleolus and Ribosome Biogenesis
               1. rRNA Transcription and Processing
               2. Ribosomal Protein Assembly
               3. Nucleolar Organization
            4. Nuclear Pores and Transport
               1. Nuclear Pore Complex Structure
               2. Nuclear Import and Export Mechanisms
               3. Ran-GTP Gradient
            5. DNA Packaging and Chromosomes
               1. Chromosome Structure and Condensation
               2. Centromeres and Kinetochores
               3. Telomeres and Chromosome Stability
         2. Cytoplasm and Organelles
            1. Mitochondria
               1. Mitochondrial Structure and Compartments
               2. Oxidative Phosphorylation
               3. Mitochondrial DNA and Inheritance
               4. Mitochondrial Biogenesis and Dynamics
            2. Endoplasmic Reticulum
               1. Rough ER Structure and Function
               2. Smooth ER Structure and Function
               3. ER Stress Response
               4. ER-Associated Degradation
            3. Golgi Apparatus
               1. Golgi Structure and Organization
               2. Protein Processing and Modification
               3. Vesicle Sorting and Trafficking
            4. Lysosomes and Peroxisomes
               1. Lysosomal Enzyme Function
               2. Autophagy Mechanisms
               3. Peroxisomal Metabolism
            5. Vesicular Transport Systems
               1. COPII and COPI Vesicles
               2. Clathrin-Mediated Transport
               3. SNARE Proteins and Membrane Fusion
         3. The Cytoskeleton
            1. Microtubules
               1. Tubulin Structure and Polymerization
               2. Microtubule Organizing Centers
               3. Dynamic Instability
            2. Microfilaments
               1. Actin Structure and Polymerization
               2. Actin-Binding Proteins
               3. Actin Networks and Bundles
            3. Intermediate Filaments
               1. Types of Intermediate Filaments
               2. Assembly and Organization
               3. Mechanical Properties
            4. Motor Proteins
               1. Kinesin Family Motors
               2. Dynein Structure and Function
               3. Myosin Types and Mechanisms
            5. Cytoskeletal Regulation and Remodeling
               1. Rho Family GTPases
               2. Cytoskeletal Cross-Talk
               3. Force Generation and Transmission
         4. The Plasma Membrane
            1. Lipid Bilayer Structure
               1. Phospholipid Composition
               2. Cholesterol and Membrane Properties
               3. Lipid Asymmetry
            2. Membrane Proteins
               1. Integral Membrane Proteins
               2. Peripheral Membrane Proteins
               3. Protein Insertion and Folding
            3. Membrane Fluidity and Dynamics
               1. Factors Affecting Fluidity
               2. Lipid Phase Transitions
               3. Membrane Curvature
            4. Membrane Domains and Rafts
               1. Lipid Raft Composition
               2. Raft-Associated Proteins
               3. Functional Significance
            5. Cell Surface Receptors
               1. Receptor Classification
               2. Ligand Binding Mechanisms
               3. Receptor Clustering and Signaling
      2. Prokaryotic Cell Structure and Function
         1. Cell Wall Composition and Structure
            1. Peptidoglycan Structure
            2. Cell Wall Synthesis
            3. Cell Wall Modifications
         2. Plasma Membrane and Periplasmic Space
            1. Membrane Composition in Prokaryotes
            2. Periplasmic Proteins and Functions
            3. Membrane Transport Systems
         3. Nucleoid and Plasmids
            1. Chromosome Organization
            2. DNA Supercoiling
            3. Plasmid Types and Functions
         4. Ribosomes in Prokaryotes
            1. 70S Ribosome Structure
            2. Ribosomal RNA and Proteins
            3. Translation Machinery
         5. Flagella and Pili
            1. Flagellar Structure and Assembly
            2. Chemotaxis and Motility
            3. Pili Types and Functions
         6. Differences Between Gram-Positive and Gram-Negative Bacteria
            1. Cell Wall Structure Variations
            2. Outer Membrane in Gram-Negative Bacteria
            3. Staining Properties and Clinical Significance
      3. The Central Dogma of Molecular Biology
         1. DNA Replication
            1. DNA Polymerases and Accessory Proteins
               1. DNA Polymerase Types and Properties
               2. Helicase and Primase Functions
               3. Single-Strand Binding Proteins
            2. Replication Origins and Forks
               1. Origin Recognition and Licensing
               2. Replication Fork Progression
               3. Termination Mechanisms
            3. Leading and Lagging Strand Synthesis
               1. Continuous vs. Discontinuous Synthesis
               2. Okazaki Fragment Processing
               3. Primer Removal and Ligation
            4. Proofreading and Repair Mechanisms
               1. Exonuclease Activity
               2. Mismatch Repair
               3. DNA Damage Response
         2. Transcription
            1. RNA Polymerases
               1. RNA Polymerase II Structure and Function
               2. Transcription Initiation Complex
               3. Elongation and Termination
            2. Promoters and Transcription Factors
               1. Core Promoter Elements
               2. General Transcription Factors
               3. Specific Transcription Factors
            3. mRNA Processing
               1. 5' Capping Mechanism
               2. Splicing and Spliceosome Function
               3. 3' Polyadenylation
         3. Translation
            1. Ribosome Structure and Function
               1. Large and Small Subunit Organization
               2. Ribosomal RNA Catalysis
               3. Ribosome Binding Sites
            2. tRNA and Aminoacylation
               1. tRNA Structure and Modifications
               2. Aminoacyl-tRNA Synthetases
               3. Codon-Anticodon Recognition
            3. Initiation, Elongation, and Termination
               1. Translation Initiation Factors
               2. Elongation Cycle
               3. Stop Codon Recognition and Release
            4. Post-Translational Modifications
               1. Phosphorylation
                  1. Kinase and Phosphatase Activity
                  2. Phosphorylation Sites and Specificity
                  3. Regulatory Functions
               2. Glycosylation
                  1. N-linked and O-linked Glycosylation
                  2. Glycosylation Pathways
                  3. Functional Roles
               3. Ubiquitination
                  1. Ubiquitin Conjugation System
                  2. Proteasomal Degradation
                  3. Non-Degradative Functions
               4. Proteolytic Processing
                  1. Signal Peptide Cleavage
                  2. Protein Maturation
                  3. Regulatory Cleavage
      4. Cell Signaling and Communication
         1. Receptors and Ligands
            1. G Protein-Coupled Receptors
               1. GPCR Structure and Classification
               2. G Protein Subtypes and Signaling
               3. GPCR Desensitization and Trafficking
            2. Receptor Tyrosine Kinases
               1. RTK Structure and Activation
               2. Dimerization and Autophosphorylation
               3. Downstream Signaling Cascades
            3. Ion Channel Receptors
               1. Ligand-Gated Ion Channels
               2. Voltage-Gated Ion Channels
               3. Channel Selectivity and Gating
            4. Intracellular Receptors
               1. Nuclear Hormone Receptors
               2. Steroid Hormone Signaling
               3. Gene Expression Regulation
         2. Signal Transduction Pathways
            1. MAPK/ERK Pathway
               1. Ras Activation and Regulation
               2. MAPK Cascade Components
               3. Pathway Specificity and Cross-Talk
            2. PI3K/AKT Pathway
               1. PI3K Activation and PIP3 Generation
               2. AKT Targets and Functions
               3. PTEN and Pathway Regulation
            3. JAK/STAT Pathway
               1. Cytokine Receptor Activation
               2. JAK Phosphorylation and STAT Recruitment
               3. STAT Dimerization and Nuclear Translocation
            4. Notch and Wnt Signaling
               1. Notch Receptor Processing
               2. Wnt/β-Catenin Pathway
               3. Developmental and Stem Cell Roles
         3. Second Messengers
            1. Cyclic Nucleotides
               1. cAMP Synthesis and Degradation
               2. cGMP Signaling
               3. Protein Kinase A and G
            2. Calcium Ions
               1. Calcium Release from Internal Stores
               2. Calcium-Binding Proteins
               3. Calcium Pumps and Exchangers
            3. Inositol Phosphates and Diacylglycerol
               1. PLC Activation and IP3 Generation
               2. DAG and Protein Kinase C
               3. Calcium Mobilization
         4. Cellular Responses to Signals
            1. Gene Expression Changes
               1. Transcriptional Activation and Repression
               2. Chromatin Remodeling
               3. MicroRNA Regulation
            2. Cytoskeletal Rearrangement
               1. Actin Polymerization and Depolymerization
               2. Cell Shape Changes
               3. Migration and Adhesion
            3. Cell Proliferation and Differentiation
               1. Cell Cycle Entry and Progression
               2. Growth Factor Requirements
               3. Differentiation Programs
            4. Apoptosis Induction
               1. Death Receptor Signaling
               2. Mitochondrial Pathway
               3. Caspase Activation Cascades
      5. The Cell Cycle and Its Regulation
         1. Phases of the Cell Cycle
            1. G1 Phase
               1. Cell Growth and Preparation
               2. G1/S Checkpoint Control
               3. Restriction Point
            2. S Phase
               1. DNA Replication Timing
               2. Replication Fork Dynamics
               3. S Phase Checkpoints
            3. G2 Phase
               1. Protein Synthesis and Cell Growth
               2. DNA Damage Checkpoints
               3. Preparation for Mitosis
            4. M Phase
               1. Mitotic Stages and Chromosome Dynamics
               2. Spindle Formation and Function
               3. Cytokinesis Mechanisms
         2. Checkpoints and Cyclin-Dependent Kinases
            1. G1/S Checkpoint
               1. p53 and DNA Damage Response
               2. Rb Protein and E2F Regulation
               3. CDK2 and Cyclin E
            2. G2/M Checkpoint
               1. DNA Damage and Replication Checkpoints
               2. CDK1 and Cyclin B
               3. Checkpoint Kinases
            3. Spindle Assembly Checkpoint
               1. Kinetochore Attachment Monitoring
               2. APC/C Regulation
               3. Mad and Bub Proteins
            4. Cyclins and CDK Regulation
               1. Cyclin Synthesis and Degradation
               2. CDK Inhibitors
               3. Phosphorylation and Dephosphorylation
         3. Apoptosis and Programmed Cell Death
            1. Intrinsic Pathway
               1. Mitochondrial Membrane Permeabilization
               2. Bcl-2 Family Proteins
               3. Cytochrome c Release
            2. Extrinsic Pathway
               1. Death Receptor Activation
               2. DISC Formation
               3. Caspase-8 Activation
            3. Caspase Activation
               1. Initiator and Effector Caspases
               2. Caspase Substrates
               3. Apoptosome Formation
            4. Apoptotic Morphology and Clearance
               1. Cell Shrinkage and Blebbing
               2. DNA Fragmentation
               3. Phagocytic Clearance
   2. Engineering Principles for Biological Systems
      1. Biothermodynamics
         1. Energy, Enthalpy, and Entropy in Biological Systems
            1. Thermodynamic Laws in Biology
               1. First Law and Energy Conservation
               2. Second Law and Entropy Production
               3. Third Law and Absolute Zero
            2. Biological Energy Conversion
               1. Metabolic Energy Transformations
               2. Efficiency of Biological Processes
               3. Heat Generation and Dissipation
         2. Gibbs Free Energy and Spontaneity
            1. Free Energy Changes in Reactions
            2. Standard and Physiological Conditions
            3. Coupled Reactions
               1. Energy Coupling Mechanisms
               2. ATP as Energy Currency
               3. Thermodynamic Favorability
            4. ATP Hydrolysis and Energy Transfer
               1. ATP Structure and High-Energy Bonds
               2. Phosphoryl Transfer Potential
               3. Cellular ATP/ADP Ratios
         3. Chemical Equilibrium
            1. Equilibrium Constants
               1. Relationship to Free Energy
               2. Temperature Dependence
               3. Concentration Effects
            2. Le Chatelier's Principle in Cells
               1. Metabolic Regulation
               2. Homeostatic Mechanisms
               3. Allosteric Control
      2. Transport Phenomena in Biological Systems
         1. Diffusion and Fick's Laws
            1. Molecular Diffusion in Cytoplasm
               1. Diffusion Coefficients
               2. Molecular Crowding Effects
               3. Anomalous Diffusion
            2. Diffusion Across Membranes
               1. Permeability Coefficients
               2. Lipid Solubility Effects
               3. Membrane Thickness
         2. Convection and Mass Transport
            1. Bulk Flow in Tissues
               1. Interstitial Fluid Flow
               2. Lymphatic Drainage
               3. Pressure Gradients
            2. Blood and Lymphatic Transport
               1. Cardiovascular Circulation
               2. Oxygen and Nutrient Delivery
               3. Waste Product Removal
         3. Membrane Transport Mechanisms
            1. Passive Transport
               1. Simple Diffusion
               2. Facilitated Diffusion
               3. Channel-Mediated Transport
            2. Active Transport
               1. Primary Active Transport
               2. Secondary Active Transport
               3. ATP-Driven Pumps
            3. Endocytosis and Exocytosis
               1. Receptor-Mediated Endocytosis
               2. Pinocytosis and Phagocytosis
               3. Vesicle Fusion and Secretion
      3. Biomechanics at the Cellular and Molecular Level
         1. Forces and Stresses on Cells
            1. Mechanical Force Types
               1. Shear Stress
               2. Compressive Stress
               3. Tensile Stress
            2. Cellular Response to Mechanical Stimuli
               1. Mechanotransduction Pathways
               2. Gene Expression Changes
               3. Cytoskeletal Remodeling
         2. Mechanical Properties of Biomolecules and Cells
            1. Elasticity and Viscoelasticity
               1. Elastic Modulus
               2. Viscoelastic Behavior
               3. Stress Relaxation and Creep
            2. Measurement Techniques
               1. Atomic Force Microscopy
               2. Micropipette Aspiration
               3. Optical Tweezers
               4. Magnetic Twisting Cytometry
         3. Cell Adhesion and Migration Mechanics
            1. Cell-Cell Adhesion Molecules
               1. Cadherins and Adherens Junctions
               2. Tight Junctions
               3. Gap Junctions
            2. Cell-ECM Interactions
               1. Integrins and Focal Adhesions
               2. ECM Composition and Structure
               3. Matrix Stiffness Effects
            3. Mechanisms of Cell Migration
               1. Protrusion and Adhesion
               2. Contractility and Retraction
               3. Collective Cell Migration
      4. Reaction Kinetics of Biological Processes
         1. Enzyme Kinetics
            1. Michaelis-Menten Model
               1. Enzyme-Substrate Complex Formation
               2. Steady-State Approximation
               3. Kinetic Parameters
            2. Inhibition and Allosteric Regulation
               1. Competitive Inhibition
               2. Non-Competitive Inhibition
               3. Allosteric Enzymes
            3. Multi-Substrate Reactions
               1. Sequential Mechanisms
               2. Ping-Pong Mechanisms
               3. Cooperativity
         2. Receptor-Ligand Binding Kinetics
            1. Association and Dissociation Rates
               1. On-Rate and Off-Rate Constants
               2. Binding Equilibrium
               3. Kinetic vs. Thermodynamic Control
            2. Affinity and Specificity
               1. Dissociation Constants
               2. Binding Selectivity
               3. Avidity Effects
         3. Gene Regulation Network Dynamics
            1. Feedback and Feedforward Loops
               1. Negative Feedback Control
               2. Positive Feedback Amplification
               3. Feedforward Regulation
            2. Oscillatory and Bistable Systems
               1. Biological Oscillators
               2. Bistable Switches
               3. Hysteresis and Memory