all of chapter 3 and a bit of 4

Plasma Membrane Insights

Structure

• The plasma membrane is primarily composed of a semi-permeable lipid bilayer, which serves as a barrier that separates the internal cellular environment from the external surroundings.

• The lipid bilayer is crucial for drug absorption in clinical settings, influencing how various therapeutic agents interact with the cells.

Phospholipid Characteristics

• Phospholipids, which form the fundamental structure of the membrane, are amphipathic molecules that possess both hydrophilic (water-attracting) and hydrophobic (water-repelling) components. This dual nature is essential for the formation and stability of the lipid bilayer.

• The arrangement and orientation of phospholipids are critical for membrane integrity, facilitating various membrane-based functions such as signaling and transport.

Membrane Fluidity

• Several factors affect the fluidity of the plasma membrane, including cholesterol content, fatty acid saturation, and temperature.

  • Cholesterol: It plays a pivotal role in maintaining membrane stability; while it increases rigidity, it has a nuanced interaction with unsaturated fatty acids, which introduce kinks into the lipid chains and thus enhance fluidity.

  • Temperature: Lower temperatures decrease the kinetic energy of molecules, resulting in reduced membrane fluidity. Conversely, increased temperatures can enhance fluidity, affecting the overall permeability of the membrane.

Membrane Proteins and Functions

• Membrane proteins constitute approximately 50% of the plasma membrane's mass and are divided into two categories: integral and peripheral proteins. They perform a plethora of functions, including:

  • Transport: Key players in the selective movement of substances across the membrane. This includes both ion channels for specific ion transport and transporter proteins that facilitate larger molecules.

  • Receptors: These proteins mediate cell signaling, allowing cells to respond to external stimuli and communicate with each other.

  • Enzymes: They catalyze essential biochemical reactions at the membrane surface, contributing to various metabolic pathways.

  • Structural Role: They provide structural support and maintain cell shape by anchoring to the cytoskeleton inside the cell.

  • Cell Recognition: Membrane proteins also play a vital role in identifying self vs. non-self, crucial for immune responses and tissue compatibility in transplantation.

Glycocalyx

• The glycocalyx is a carbohydrate-rich coating on the extracellular surface of the membrane, which contains glycoproteins and glycolipids. It provides protective roles and serves as a recognition site for cells, distinguishing between self and foreign entities, and playing critical roles in cellular interactions and signaling.

Cell Junctions

• Cell junctions are specialized structures that facilitate intercellular communication, sharing of materials, and help maintain the integrity of tissues. The main types include:

  • Desmosomes: Acting as anchoring junctions, they provide mechanical stability to tissues under stress, particularly in the skin and heart.

  • Tight Junctions: These junctions form a seal between adjacent cells, preventing the passage of molecules between them, crucial for barriers like the gastrointestinal tract and blood-brain barrier.

  • Gap Junctions: Composed of connexins, they allow for direct communication between adjacent cells by enabling the passage of ions and small molecules, facilitating rapid electrical signal transmission in tissues such as cardiac and smooth muscles.

Membrane Transport Mechanisms

• The plasma membrane employs various transport mechanisms to regulate the movement of substances into and out of the cell:

  • Passive Transport: This process does not require ATP and occurs down the concentration gradient. It includes diffusion (movement of small non-polar molecules) and osmosis (movement of water).

  • Active Transport: Involves the use of ATP to move substances against their concentration gradient. Examples include the sodium-potassium pump, which maintains ion gradients essential for electrical signaling in neurons.

• Osmosis: Specifically refers to the movement of water across a selectively permeable membrane, typically toward areas of higher solute concentration, thereby balancing solute levels.

• Facilitated Diffusion: Involves transport proteins to assist the movement of substances like glucose and ions across the membrane.

  • Carrier-Mediated: Uses specific carrier proteins that change shape to transport substances.

  • Channel-Mediated: Involves protein channels allowing specific ions to flow through the membrane.

• Vesicular Transport: This type of transport is vital for moving larger molecules and involves mechanisms such as endocytosis (e.g., phagocytosis for eating and pinocytosis for drinking) and exocytosis (expelling substances from the cell).

Factors Affecting Diffusion

• The rate of diffusion across membranes is influenced by several factors:

  • Concentration Gradient: The difference in concentration of a substance between two areas is a driving force for diffusion; substances will naturally move from regions of high concentration to low concentration.

  • Particle Size: Smaller particles generally diffuse more rapidly than larger ones.

  • Temperature: Higher temperatures increase the energy and speed of molecular movement, thus enhancing diffusion.

  • Distance: The thicker the membrane, the longer it takes for substances to diffuse across it, highlighting the importance of membrane surface area in diffusion efficiency.

Membrane Permeability

Diffusion and Osmosis

The discussion starts with the critical influence of membrane permeability on diffusion and osmosis, two essential processes in cellular function and homeostasis.

Truly Permeable Membrane

• A truly permeable membrane is one that permits the passage of both water and solutes. This characteristic is fundamental in defining osmolarity, which is the total solute concentration in a solution.

• Higher osmolarity correlates with a lower concentration of free water molecules, as these water molecules engage with solute particles to form solvation shells, decreasing the water available for movement.

• Equilibrium: At equilibrium, water will move from regions of lower osmolarity (less concentrated solute solutions) to regions of higher osmolarity (more concentrated solute solutions), striving to balance solute concentrations between compartments and adjusting their volumes accordingly.

Selectively Permeable Membrane

• In contrast, a selectively permeable membrane only allows the passage of water while restricting solutes, thereby facilitating osmosis, which is the passive movement of water towards the area of higher solute concentration to equilibrate solute levels.

• An important mnemonic to understand this is "water goes for the saltiness," indicating that water migrates toward higher solute concentrations during osmosis.

Osmotic Pressure

• Osmotic pressure is defined as the force exerted by the water moving into a cell by osmosis, which increases in direct relation to osmolarity.

• The significance of osmotic pressure lies in its physiological effects, where a chamber with a higher osmolarity draws water from an adjacent chamber of lower osmolarity, thereby influencing the volume and functional integrity of the cells involved.

• Remember the key concept: "Solutes suck"—as osmolarity rises, so does osmotic pressure, which can have profound effects on cell volume and function.

Tonicity of a Solution

• Isotonic Solution: In an isotonic solution, there is no net movement of water; the concentration of solutes remains equal inside and outside the cell, maintaining cell stability.

• Hypertonic Solution: A hypertonic solution outside the cell contains a higher concentration of solutes, which results in water leaving the cell, a process that can lead to cell shrinkage or crenation.

• Hypotonic Solution: Conversely, in a hypotonic solution, there is a lower concentration of solutes outside the cell, leading to water entering the cell, which may ultimately result in cell swelling and possible lysis (hemolysis).

• Clinically, isotonic solutions are crucial for intravenous (IV) fluid replacement, as they help maintain cellular integrity without causing deformation due to osmotic pressures.

Cellular Sensitivity

• Animal cells are particularly sensitive to osmotic fluctuations because they lack a rigid cell wall; this makes them more susceptible to the effects of tonicity compared to plant cells, which possess cell walls that provide structural support and protection against osmotic imbalances.

• Hence, understanding osmolarity and tonicity is vital, especially in a clinical context, to prevent cell damage or dysfunction.

Active Transport Processes

Overview

• Active transport refers to the cellular mechanisms that require energy (ATP) to move substances against their concentration gradients, unlike passive processes that rely solely on diffusion and osmosis.

• Types of Active Processes: Includes both primary active transport and vesicular transport, involving either direct energy use or the formation of membrane-bound vesicles.

Primary Active Transport

• This process directly utilizes ATP for the transport of molecules, crucially establishing ion gradients necessary for cellular operations. A prime example is the sodium-potassium pump, which exchanges three sodium ions out of the cell for two potassium ions into the cell, utilizing ATP to maintain homeostasis.

Secondary Active Transport

• Secondary active transport moves substances against their gradient using the energy generated by primary active transport mechanisms. This can involve co-transport, where the movement of one substance facilitates the simultaneous movement of another.

Active Transport Mechanisms

• Symport: In this mechanism, two substances are transported in the same direction across the membrane.

• Antiport: This involves the transport of two substances in opposite directions; one enters the cell while another exits.

Sodium-Potassium Pump

• The sodium-potassium pump is essential for generating and maintaining ion gradients across the cell membrane, which are critical for various physiological processes, including action potentials in neurons.

• The resting membrane potential of a cell, which usually falls between -50 to -100 mV depending on cell type, is established through a balance of potassium efflux and sodium influx, leading to a stable negative charge within the cell.

Chemical Signaling

Overview

• This section explains how ligands, which serve as chemical messengers, bind to specific receptors on target cells to induce tailored cellular responses.

• Types of Ligands: These may include neurotransmitters, hormones, or other signaling molecules that initiate and propagate biological signals.

Receptors

• Receptors are specialized binding sites for ligands; interestingly, the same ligand can trigger diverse effects based on receptor subtype and the coupling mechanisms intracellularly, tailored to the cell type involved.

G-Protein Coupled Receptors (GPCRs)

• GPCRs play a vital role in a multitude of signaling pathways by activating intracellular second messengers, such as cyclic AMP (cAMP), upon ligand binding.

• There are stimulatory (GS) and inhibitory (GI) G-proteins, which can have different effects on the cell's response, thus influencing physiological outcomes significantly.

Introduction to Cellular Communication

Importance of Cell Signaling in the Human Body

Cell signaling is crucial for coordinating biological processes in multicellular organisms. Cells communicate to regulate vital functions such as growth, immune responses, and homeostasis. Effective signaling is essential for cellular responses to environmental changes and for maintaining physiological equilibrium.

Distinction: Water-soluble vs Lipid-soluble Ligands

• Lipid-soluble ligands: These molecules, such as steroid hormones, can easily diffuse across the lipid bilayer of the plasma membrane. Once inside the cell, they bind to specific intracellular receptors, often leading to direct regulation of gene expression. This mechanism allows for a rapid response to hormonal changes in the body.

• Water-soluble ligands: These include peptide hormones and neurotransmitters, which cannot cross the plasma membrane. Instead, they bind to receptors on the cell surface, initiating a cascade of intracellular signaling events via second messengers like cyclic AMP (cAMP) and calcium ions. This pathway amplifies the signal and allows for a fast cellular response.

The Cell Cycle

Definition

The cell cycle is a life cycle of a cell, representing a series of phases that a cell undergoes from the completion of cell division to the beginning of its next division. It is fundamentally important for organism growth, maintenance, and repair.

Purpose of Cell Division

Cell division serves several essential purposes:

• Growth: Enables organisms to grow in size.

• Repair: Facilitates the repair of damaged tissues by replacing dead or dysfunctional cells.

• Reproduction: In unicellular organisms, it allows for replication and continuation of the species.

Phases of the Cell Cycle

1. Interphase (major period): Accounts for the majority of a cell's life and is subdivided into three main phases:

   • G1 Phase (Gap 1): Cells grow and perform their normal functions, synthesizing proteins and organelles.

   • S Phase (Synthesis): DNA replication occurs, ensuring that each daughter cell receives an identical set of chromosomes.

   • G2 Phase (Gap 2): Cells prepare for mitosis, producing proteins and organelles required for division, and checking for DNA errors.

2. M Phase (Mitotic Phase):

   • Mitosis: The process of nuclear division consisting of four stages: Prophase, Metaphase, Anaphase, and Telophase (collectively known as PMAT).

   • Cytokinesis: The division of the cytoplasm and organelles between the two daughter cells, completing the cell division process.

Checkpoints in the Cell Cycle

• G1 Checkpoint: Evaluates the cell's size, nutrient status, and DNA integrity before committing to DNA replication. Cells with irreparable damage may enter a resting state known as the G0 phase.

• G2 Checkpoint: Ensures that DNA has been replicated accurately and is free from damage before commencing mitosis.

• M Checkpoint: Assesses whether all chromosomes are correctly attached to the spindle apparatus, ensuring accurate chromosome separation.

Importance of Cell Division

Cell division rates vary significantly among different cell types:

• Epithelial cells: High regeneration potential, continuously replacing themselves due to frequent wear and tear.

• Cardiac and nervous cells: Exhibit low regeneration rates. Cardiac muscle cells enter a non-dividing state post maturation, meaning damage incurs lasting effects, often leading to scar tissue formation that lacks functional capacity.

DNA Replication in the S Phase

Essential Steps for DNA Replication

1. Uncoiling: DNA helicases unwound the double helix at multiple origins of replication, forming replication forks to accelerate the process.

2. Separation: Hydrogen bonds between complementary nucleotide base pairs break, creating replication bubbles.

3. Assembly: DNA polymerases synthesize new strands by adding complementary nucleotides (A with T, and C with G), ensuring accurate base pairing and replication.

4. Restoration: DNA ligase seals any gaps created on the lagging strand by joining Okazaki fragments, finalizing the newly synthesized DNA strand.

Semi-Conservative Replication

In the semi-conservative replication model, each newly formed DNA molecule consists of one original parental strand and one newly synthesized strand. This mechanism preserves the genetic integrity and ensures variation is minimized during cell division.

Stages of Mitosis

• Prophase: Chromatin condenses into visible chromosomes. The mitotic spindle begins to form, and the nuclear envelope disintegrates.

• Metaphase: Chromosomes align along the equatorial plane of the cell, and spindle fibers connect to kinetochores on chromosomes.

• Anaphase: Sister chromatids are pulled apart towards opposite poles of the cell, ensuring each new daughter cell receives an identical set of chromosomes. Cytokinesis begins.

• Telophase: Chromatids unwind back into chromatin, nuclear envelopes reform around each pole of separated chromosomes, restoring the nucleus in each daughter cell.

Protein Synthesis: Flow of Genetic Information

Process Involves Transcription and Translation

• Transcription: The process where the genetic information encoded in DNA is transcribed into messenger RNA (mRNA). This occurs in the nucleus and involves several steps:

  • Initiation: RNA polymerase binds to the promoter region of a gene, unwinding the DNA double helix.

  • Elongation: RNA polymerase synthesizes the mRNA strand by sequentially adding complementary RNA nucleotides (A with U, C with G).

  • Termination: RNA polymerase reaches a termination sequence, leading to the release of the newly formed mRNA molecule, which undergoes further processing (such as capping and polyadenylation).

• Translation: The process where mRNA is translated into a protein at ribosomes:

  • Involves initiation, elongation (which includes three steps: codon recognition, peptide bond formation, and translocation), and termination upon reaching a stop codon.