Cell Biology: Structure and Function

Cell Fundamentals

• Cells make up all living things and are the fundamental structural and functional units of life
• Bacteria, protozoans, fungi, plants and animals are major classifications of living organisms containing cells
• Some organisms like bacteria and protozoans are unicellular
• Animals, including humans, are multicellular, with the adult human body containing around 100 trillion cells
• Cells need basic resources, and organs give these to cells (like oxygen, food, and waste disposal)

Cell Types and Organization

• There are roughly 200 kinds of cells in the human body
• Tissues form when identical cells perform a common purpose
• Organs form when different tissues combine to serve a shared purpose
• Systems form when groups of organs with related functions work together
• Understanding of cells has evolved from simple membranous sacs to far more complex systems
• Knowledge of cellular organelles and how they function is key to physiology
• Healthy cells are critical to overall health, where all physiological processes relate back to cellular functions

Cell Study Milestones

• Robert Hooke discovered that cork was made of tiny compartments in 1665 while using a microscope
• Hooke called these compartments "cells" (from the Latin word for small room)
• Anton Van Leeuwenhoek saw bacteria, sperm, and red blood cells in 1672
• Robert Brown discovered that cells had a central nucleus in 1831

Cell Theory

• M.J. Schleiden and Theodore Schwann created the cell theory in 1838
• Cell theory includes that every organism has cells
• Cell theory includes that cells are the structural and functional unit of life
• Cell theory includes that all cells come from other existing cells

Cell Diversity

• Cells vary in shape and size
• Nerve cells can extend several centimeters
• Muscle cells are elongated
• Ostrich eggs are the largest known cells at 75mm

Cell Structure

• A cell consists of a cell body that is contained by a cell membrane
• A cell body is divided into the nucleus and cytoplasm
• Cell structures are studied based on the cell membrane, cytoplasm, and nucleus

Cell Membrane Functions

• The cell membrane's main job is to protect the cell and its contents inside
• The cell membrane is selectively permeable
• The cell membrane helps bring nutrients inside of cells
• The cell membrane is responsible for removing waste
• The cell membrane helps make gas exchanges more efficient
• The cell membrane shape and size is also influenced by the cell membrane

The Cell Membrane

• The cell membrane is a protective layer around a cell body and is also called the plasma membrane or plasmalemma
• It separates the extracellular fluid (ECF) from intracellular fluid (ICF)
• It acts as a semipermeable barrier, allowing certain substance exchanges between the ECF and ICF
• The membrane's thickness is between 7.5 and 10 nanometers

Cell Membrane Composition

• The cell membrane consists of 55% proteins, 40% lipids, and 5% carbohydrates
• James F Danielli and Hugh Davson proposed the first basic structural model of the membrane, called the Danielli Davson model in 1935
• The Danielli Davson model described a lipid sandwich with protein coverage
• JD Robertson proposed the 'Unit membrane model' in 1957, replacing the Danielli-Davson model on electron microscopic studies
• The Fluid mosaic model was proposed in 1972 by Singer and Nicholson, and is widely accepted today

Fluid Mosaic Model

• The plasma membrane is a three-layered structure consisting of a phospholipid bilayer with embedded globular proteins
• Every phospholipid has two-ends consisting of a hydrophilic head and a hydrophobic tail end
• The tail end of the phospholipid is repelled by water and is hydrophobic
• The head end of the phospholipid is water-attracting and hydrophilic
• Membrane proteins are arranged as peripheral (extrinsic) and integral (intrinsic) proteins
• Peripheral proteins are located on the outer and inner surfaces
• Integral proteins can penetrate the lipid bilayer partially or wholly

Lipid Layers

• The lipid layer comprises a thin layer of phospholipids and cholesterol
• Phospholipids contain phosphorus and fatty acids, including aminophospholipids, sphingo-myelins, phosphatidylcholine, phosphatidyletholamine, phosphatidylglycerol, phosphatidylserine, and phospha tidylinositol
• Phospholipids are arranged in two layers with a polar head and a non-polar tail
• The hydrophilic head is soluble, while the hydrophobic tail repels water and meets in the membrane's center
• Head portions on the outer layer are oriented toward the ECF, and heads of the inner layer towards the ICF (cytoplasm)
• Cholesterol molecules are situated between phospholipids
• Cholesterol 'packs' phospholipids to add structural integrity

Function of Lipid Layers

• The lipid layer serves as a semipermeable barrier
• The lipid layer only allows fat-soluble substances, like oxygen, carbon dioxide and alcohol, to pass through
• Water-soluble substances like glucose, urea, and electrolytes are unable to pass through it

Protein Layers

• Protein layers flank each side of the central lipid layer
• Protein layers consist mainly of glycoproteins
• Protein layers cover and protect the central lipid layer from damage
• Proteins are categorized as either integral (transmembrane) or peripheral

Integral Proteins

• Integral proteins span the entire membrane and strongly bind with it
• They include cell adhesion proteins, cell junction proteins, some carrier and channel proteins, hormone receptors, antigens, and enzymes

Peripheral Proteins

• Peripheral proteins are partially embedded in the membrane's outer and inner surfaces
• Peripheral proteins are attached to integral proteins or the lipid layer
• Peripheral proteins are easily separated from the membrane and consist of cytoskeleton proteins, some carrier proteins and enzymes

Functions of Membrane Proteins

• Integral proteins maintain the cell membrane's structural integrity and attach cells
• Channel proteins mediate diffusion of water-soluble substances
• Carrier proteins help actively or passively transport substances
• Acting as pumps, carrier proteins actively transport ions
• Receptor proteins bind hormones and neurotransmitters
• Enzymes regulate chemical reactions
• Antigens induce antibody production

Cell Membrane Carbohydrates

• Some carbohydrates attach to proteins to form glycoproteins while others attach to lipids to form glycolipids
• Carbohydrates on the cell’s surface form a glycocalyx, a thin sugar coat
• Having a negative charge keeps similarly charged substances from passing through the cell membrane
• Glycocalyx helps cells attach to one another and can be receptors for hormones

Transport Mechanisms

• A cell membrane uses transport mechanisms to get essential nutrients and substances while getting rid of harmful waste products
• The lipid and protein structure of the cell membrane are the reason why this transport is possible between the ECF and ICF

Transport Types

• Passive and active are the two main transport mechanisms for moving substances across plasma membranes

Passive Transport

• Moving substances along a concentration or electrical gradient without requiring energy
• Substances move from high to low concentration areas

Diffusion

• Diffusion is the movement down a concentration gradient and can be simple or facilitated depending on whether it goes through either a lipid layer or protein channel using carrier proteins

Simple Diffusion

• Substances move through either the lipid or protein layer of the cell membrane
• The lipid/fat soluble substances like oxygen, carbon dioxide and alcohol use the lipid layer
• Electrolytes use the protein layer

Protein/Ion Channels

• Integral proteins form pores or channels through the lipid layer for water, electrolytes, and other substances to pass
• These channels are selective, permitting only specific ions
• Channels are named after the ion they allow to pass, like sodium or potassium channels

Channel Regulation

• Some channels remain open continuously and are called ungated channels, while others are closed and open only when necessary and are called gated channels
• Gated channels fall into three categories, voltage-gated, ligand-gated, and mechanically gated

Gated Channel Types

• Voltage-gated channels: they open due to changes in electrical potential; for example, calcium channels at the axon terminal in neuromuscular junctions
• Ligand-gated channels: they open in the presence of hormones called ligands. For example, acetylcholine opens sodium channels at the neuromuscular junction
• Mechanically gated channels: they open due to mechanical factors, such as pressure receptors, deformation of core fibers, or receptor potential development

Facilitated Diffusion

• This involves water-soluble substances being transported with the help of carrier proteins
• Substances are transported faster than in simple diffusion
• Glucose and amino acids will be transported by facilitated diffusion, and these molecules bind with a carrier protein, resulting in a change and enabling movement

Special Passive Transport

• Bulk flow, filtration, and osmosis are various types of passive transport

Bulk Flow

• Large quantities of substances move from high to low pressure regions due to a pressure gradient
• This is best shown through gas exchange in the lungs
• Oxygen in the alveoli moves to the blood , and carbon dioxide in the blood air moves into the alveoli

Filtration

• The movement of water and solutes from an area of high hydrostatic pressure to low hydrostatic pressure
• Hydrostatic pressure is due to the weight of a fluid pushing down
• Seen at the arterial end of capillaries and in the kidney glomeruli

Osmosis

• Water or any solvent moves from low to high solute concentration through a semipermeable membrane
• This membrane allows only water or solvents through, creating a concentration difference and what is called osmotic pressure
• When water moves, solutes dilute within the solvent, creating a pressure called osmotic pressure

Active Transport

• Involves movement of substances against a chemical, electrical, or electrochemical gradient requiring energy
• The needed energy is gained by breaking down high-energy chemicals like ATP
• A substance makes contact with the membrane's carrier proteins forming a substance-protein complex that then travels to the inner layer and is released
• After release inside the cell, the carrier is then moved back to the outside of the cell to repeat the process

Carrier Protein Types

• Uniport carriers: They transport only one substance in a single direction, acting as a uniport pump
• Symport or antiport: Transports two substances at a time
• Symport moves two substances in same direction
• Antiport moves two substances in opposite directions

Substances Actively Transported

• Actively transported substances may be either ionic (e.g., sodium, potassium, calcium) or non-ionic (e.g., glucose, amino acids, urea)

Transport Types

• Primary and secondary transport are the two main types

Primary Active Transport

• Energy comes directly from ATP breakdown, used to transport substances like sodium, potassium, calcium, etc
• A major example is the sodium-potassium pump which uses the protein to transport sodium and potassium through the membrane
• The Sodium-Potassium Pump moves sodium out of the inside while moving potassium in, which is present in every cell of the body

Secondary Active Transport

• Sodium ions are used to transport a substance by a common protein
• Another substance is transported by the same protein together with sodium, which is coupled
• This can happen in the same direction(symport) or the opposite(antiport) directions

Sodium Cotransport

• Another substance and sodium are transported using the same carrier in the same direction
• ATP is used in sodium's movement, and the energy is used for movement of other substances
• Chloride, glucose, ions, amino acids, and urate are carried by sodium cotransport
• An example substance is glucose absorbed from the intestine and reabsorbed in renal tubule

Sodium Counter Transport

• Carrier proteins exchange sodium ions for another substance that are going across the cell membrane
• An example would be the sodium calcium counter transport happening between sodium and calcium with a carrier protein

Special Types of Active Transport

• This relates to primary and secondary transport are called vesicular transport

Endocytosis

• Macromolecules move into cells; it is a transport mechanism in which larger molecules cannot pass through the membrane either actively or passively
• Pinocytosis is a process by which macromolecules like antigens and bacteria are taken into the cells, is also known as cell drinking
• Phagocytosis, which is when cells engulf bigger molecules like other bacteria or foreign matter, is also called cell eating
• Receptor-mediated Endocytosis, uses proteins to transport large macromolecules

Pinocytosis Steps

• Macromolecules present in the fluid bind to the surface of the cell membrane
• Cell membrane surrounds the molecules during evagination
• The membrane surrounds the molecules so they can become vesicles
• The molecules are engulfed by the vesicle and converted into vacuoles called endosomes
• Endosomes enter inside the cell
• Secondary lysosomes are formed when primary lysosomes come into contact with the endosome
• Contents are digested and dissolved from the hydrolytic enzymes located in the secondary lysosome

Phagocytosis

• Involves cells engulfing other entities
• Includes cells such as monocytes, tissue macrophages, and neutrophils
• Macrophages send cytoplasmic extensions (pseudopodium) to surround matter
• Once surrounded, the matter is pulled into the cell like a vacuole called a phagosome
• The phagosome enters the cell where lysosomes join it
• After the joining of the cells happens the material starts to degrade from the hydrolytic contents

Receptor Mediated Endocytosis

• Uses receptor proteins to help move matter like macromolecules
• There are pits that contain clathrin proteins
• Together with the proteins this becomes what is called a receptor coated pit
• Receptor-coated pits help in receptor mediated endocytosis

Exocytosis

• Involves substances released from cells
• Secretory vesicles fuse with a cell membrane, releasing contents out of the cell

Transcytosis

• Move extracellular macromolecules: a transport system where matter enters on the cell side, traverses, and proceeds to exit the opposite location
• A cell uses invagination to collect matter and make it a vesicle, moving it across and releasing again by means of exocytosis on the other side
• Caveolin rather than clathrin is the protein for receptor coated pits
• Also known as "vesicle trafficking" or "cytopempsis"

Cell Death

• Cell death is when cells stop doing what they are supposed to
• Death is eventual for all life at individual or cellular levels
• Results from either programmed cell death, disease, injury, or death of organism the cell is apart of

Apoptosis

• A form of programmed cell death, also called ‘cell suicide’, and aids in getting rid of unwanted cells
• Series of events that are produced by dedicated gene products
• This happens when cells are being developed
• Necrosis does create inflammation around areas the death is occurring

Apoptosis Triggers

• Triggered by either withdrawal from signals for survival or getting signals to die

Negative Signal

• Signals are the external or internal stimuli that cause apoptosis
• Brought about by: Damage of DNA, Cellular stress, Viral infection, Increase in the concentration of intracellular oxidants, Exposure to agents like chemotherapeutic drugs, X-rays, ultraviolet rays and the death-receptor ligands (TNF α, TNF β and Fas ligand).

Mitochondria's Role

• Caspases are normally inactive and they are proteases
• Mitochondria release Cytochrome C and SMAC (Second mitochondria-derived activator of caspases) after the stimuli
• Cytochrome C and SMAC then turn caspases on
• The creation of the cytochrome, SMAC, and AIF is called the apoptosome

Apoptosis Process

• Cyto-skeleton proteins are digested, ultimately shrinking and rounding a cell
• Chromatin undergoes degradation and condensation
• DNA is cleaved apart
• Discontinuities are created at the membrane forming a bubbled appearance
• Cells separate into fragments of intracellular and organelle matter
• Cell fragments are engulfed by phagocytes

Abnormalities

• Abnormalities are caused by too much or too little apoptosis occurring
• Increased apoptosis can cause ischemic related injuries, autoimmune diseases, neurodegenerative diseases
• With decreases of the process you can get things like autoimmune lymphoproliferative syndrome (ALPS) or Cancer
• Cancer and Autoimmune lymphoproliferative syndrome (ALPS) are due to too little apoptosis being done

Necrosis

• 'Cell murder" from unexpected accidental damage that causes cell death in the body
• Cells release harmful substances after dying that can cause inflammation
• Common Causes: Injury, Cancer, Infections, Infarction and Inflammation

Necrosis Cell Processes

• Formation of small blebs
• Changes in nuclear structure
• The various blebs fused and become larger
• No organelles in the blebs
• Rupture of cell membrane releasing content of cells
• Organelle are non functional
• Induction of inflammation
• Tissue damage

Consequences of Necrosis

• Immunological reactions occur to subcellular components
• Followed up by acute or chronic inflammation
• The body goes through lysing and absorbing of material
• Isolation of material
• Cavity formation
• Encapsulation
• Calcification

Homeostasis

• In response to the external environment, homeostasis is the ability for an organism to adjust to stay stable
• This ability is done through the endocrine and nervous system

Harvard Professor Cannon

• Coined the term Homeostasis in 1930
• The great biologist of 19th century Claude Bernard notified the importance of the internal environment
• Normal healthy living achieved in large organisms by internal environment staying in physiological limits

Homeostasis Functions

• Homeostasis works by maintaining balance within the body with regulating factors like temperature, pH levels, salt and blood sugar concentration

Homeostatic Components

• Homeostasis includes four components: -Sensors/Detectors: They find deviations -Message transmission -Transmission of the message information sent to effectors to make the corrective action -Effectors, that make the appropriate reactions

Action

• Normalcy by adjusting through inhibiting and reversing a change with supporting or accelerating one; is achieved through feedback signals
• Is achieved through feedback signals
• This feedback is passed from the input back to the output
• Feedback includes either negative and positive

Negative Feedback

• Arresting a change or reversing flow in system
• Leads to stabilization with homeostasis being maintained

Positive Feedback

• Leads to increased change in system
• Significance is particularly felt in the emergencies