Physiology 1.04 PDF

Physiology 1.04 Foundational Physiology Cell Membranes in Physiology BMS 100 Learning Outcomes Describe the structural components of the cell membrane, including: Basic structure and function of the following lipid components: phospholipids, cholesterol, sphingolipids The b...

Physiology 1.04 Foundational Physiology Cell Membranes in Physiology BMS 100 Learning Outcomes Describe the structural components of the cell membrane, including: Basic structure and function of the following lipid components: phospholipids, cholesterol, sphingolipids The basic types, structures, and functions of membrane proteins. Basic structure of the phospholipid bilayer Describe the function of the plasma membrane, including The barrier function of the phospholipid bilayer for molecular partitioning and homeostasis Types of transport across the plasma membrane Define the forces at play across the cell membrane, including diffusion & osmosis and relate them to types of transport across the plasma membrane. Outline the structure, function, and energy use of the Na +/K+ ATPase and describe how this helps maintain cellular integrity. Role of the cell membrane in cell signaling Describe the common features & functions of the cytoskeleton Describe the structure and specific functions of the following: Microfilaments Microtubules Intermediate filaments Describe the cellular motors that associate with F-actin and microtubules Overview – Cell Membranes lipid components of the cell membranes: phospholipids, cholesterol, sphingolipids Types of membrane proteins and their functions Comparison of the plasma membrane and the endomembrane system The cytoskeleton – microfilaments, microtubules, and intermediate filaments Functions of cell membranes Molecular partitioning and homeostasis Transport Movement Cellular integrity Cell signaling The Cell Membrane – General Structure Each component of the cell membrane contributes to its function in a unique way Anatomy and Physiology – 2nd ed. p. 84, fig. 3.4 https://openstax.org/books/anatomy-and-physiology-2e Lipid components Glycerophospholipids ▪ Let’s briefly review the components of glycerophospholipids ▪ Most common glycerophospholipids in the cell membrane are: Phosphatidylcholine, phosphatidylethanolamine, & phosphatidylserine Phosphatidylinositol is less common, but has important signalling role  Lipid components Sphingolipids ▪ Slightly different shape can decrease membrane fluidity ▪ Carbohydrate headgroups can serve a number of functions Cellular signaling – formation of lipid rafts and myelin (more later) Contribution to the glycocalyx  Lipid components Glycocalyx ▪ Carbohydrates covalently attached to protein and lipid components of the cell membrane form the glycocalyx ▪ More notable on the outer leaflet of the cell membrane ▪ Many protective structural and signaling functions  Lipid components Cholesterol ▪ Belongs to the isoprenoid class of lipids ▪ Intercalates between phospholipids with the –OH closest to the aqueous interface ▪ Cholesterol helps to stabilize membrane fluidity  Structure and function – membrane lipids Amphipathic nature of lipids in the Phospholipid cell membrane → formation bilayer bilayers ▪ Thermodynamically favourable – hydrophobic tails interact with each other and hydrophilic heads interact with the aqueous environment The phospholipid bilayer is an effective barrier to which types of molecules?  Structure and function – membrane lipids The integrity of the plasma membrane is key to the survival and normal function of the cell: ▪ Maintaining ionic and fluid homeostasis ▪ Keeping vital molecules needed for cellular metabolism within the cell ▪ Cellular movement and shape are accomplished with interactions between the cell membrane and the cytoskeleton The membrane system – plasma membrane, endomembrane system, and all membrane-bound organelles – have unique functions ▪ The membrane is the most important way that these functions remain sequestered with these organelles Loss of membrane integrity threatens cell survival ▪ The cell membrane can “re-seal” with minor mechanical disruptions – bilayers are thermodynamically favourable ▪ However, severe mechanical or metabolic stresses can lead to degradation  Structure and function – membrane lipids Membranes inside the cell don’t need to: ▪ Signal to other cells ▪ Protect cells from harsh environments or microbes ▪ Form a glycocalyx Therefore no need for sphingolipids Much less cholesterol in the membranes of organelles ▪ Perhaps less need for alterations in membrane fluidity? Anatomy and Physiology – 2nd ed. p. 92, fig. 3.13 https://openstax.org/books/anatomy-and-physiology-2e  Structure and function – membrane lipids Which intracellular membrane-bound components might have more cholesterol and/or sphingolipids? Why might this be? Hint… how do you make more plasma membrane? Anatomy and Physiology – 2nd ed. p. 92, fig. 3.13 https://openstax.org/books/anatomy-and-physiology-2e  Membrane proteins Wide range of functions: ▪ Signaling ▪ Protection ▪ Transport & General ▪ Structure & Movement Homeostasis The membrane and cellular homeostasis Key forces at work across the cell membrane: Diffusion ▪ The movement of molecules from a region of higher concentration to lower concentration Osmosis ▪ Diffusion of water through a semi-permeable membrane Semi-permeable = it allows water to pass through, but is impermeable to at least one solute Osmosis – U-tube Imagine the model at the right, filled with pure water, with a semi-permeable membrane at the base ▪ The membrane is permeable to water, but nothing else Water is free to move across the membrane, and thus there is no difference between its “concentration” across either side of it  Osmosis – U-tube Let’s add some sugar to the right side – the membrane is impermeable to the sugar 1. 2. What happened? Why? Diffusion & Osmosis - Relevance The cell membranes are semi-permeable – water + many other solutes can traverse them ▪ Most cells express many aquaporins in the plasma membrane leading to higher water conductance ▪ Membranes are impermeable to many solutes - especially larger ones The interior of the cell has a higher concentration of large solutes than the exterior, therefore… … the plasma membrane must expend energy to regulate solute concentration and cell volume The plasma membrane and organelle membranes rely on concentration gradients for important signaling and metabolic functions (more later) Importance of the Na+/K+ ATPase The Na+/K+ ATPase is a key plasma membrane transporter – each “cycle” of transport involves ▪ 3 Na+ out of the cytosol → into the extracellular fluid (ECF) ▪ 2 K+ into the cytosol (ICF) → out of the ECF ▪ Hydrolysis of one ATP → ADP + Pi Responsible for up to 30% of ATP use in many cells ▪ Establishes a gradient of sodium and potassium across the membrane Prevents cell swelling due to osmosis Establishes a gradient of charge across the membrane (more next day) Na+ gradient can be used to transport other substances across the membrane Na+/K+ pump and ICF/ECF fluid Importance of the Na+/K+ ATPase Prevention of cellular swelling ▪ As soon as ATP levels fall to 10% of normal levels, cells start to swell Why? Important cellular signaling events can depend on movement of charged particles (Na+, K+, or others) across the membrane ▪ Changes the charge across the membrane and can change cellular activity – more later Since [Na+] in the ECF is high, there is a diffusional force that drives it into the cell ▪ This force can be used to transport other substances into or out of the cell Co- or countertransport Transport and the Cell Membrane Transport can be passive ▪ In this situation, molecules move across the membrane from high to low concentration, driven by diffusion ▪ Channels or transporters are required unless the molecule is small and hydrophobic (i.e. carbon dioxide, oxygen) Transport can be active – energy is required ▪ Energy from the hydrolysis of ATP ▪ Energy from the gradient of another molecule ▪ Either way, requires an integral membrane protein  Type of Process Example transport Active A protein moves a substance(s) across a membrane Na+/K+ ATPase transport against a concentration gradient using ATP Passive A protein forms a channel that allows a substance Aquaporins transport across the membrane, along its concentration gradient Facilitated A protein carrier binds to a substance and Glucose transport transports it across a membrane, allowing it to transporter follow its concentration gradient (GLUT) Co- The transport of two substances (X and Y) are Sodium-glucose transport coupled using the same protein. The concentration co-transporter gradient of X favours movement into the cell – Y is “pulled” along, even if the gradient for Y does not (SGLT-1 and -2) favour cell entry Counter- X and Y move in opposite directions across the cell Cl-/HCO3 transport membrane – the gradient of one of the molecules counter- supplies the energy to drive the transport transporter Examples FYI for now  Label the picture below with the following types of transport: active, passive diffusion, facilitated diffusion, co-transport, counter-transport Other Cellular Membranes and Gradients For each organelle, list at least one specific way that the membrane surrounding the organelle is important to the cell Why not just have that organelle “open” to the cytosol? Plasma Membrane and Signaling All cells respond to a wide range of extracellular signals ▪ Growth factors and “anti-growth” signals ▪ Signals that change cellular activity (hormones, neurotransmitters) Most of these signals involve the binding of a chemical (the signal) to a high-affinity protein receptor on the cell membrane → a signal that’s propagated into the cytosol Most of these receptors have: ▪ hydrophobic domains that extend through the lipid bilayer (usually an alpha-helix) ▪ An extracellular domain that binds to the message (i.e. hormone) ▪ an intracellular domain that amplifies the signal A Typical Extracellular Signal Whether the cell responds to the signal (the hormone) depends on whether it expresses the receptor Steps FYI for now  Membrane proteins Wide range of functions: ▪ Signaling ▪ Protection ▪ Transport & General ▪ Structure & Movement Homeostasis Anatomy and Physiology – 2nd ed. p. 84, fig. 3.4 https://openstax.org/books/anatomy-and-physiology-2e Membrane proteins - structure Membrane proteins are important to the overall structure of the cell ▪ Can link the cell membrane to important extracellular structures ▪ Can link the cell membrane to the cytoskeleton Membrane proteins that link the cell to extracellular structures (ECM, other cells) are known as junctions  Tight junctions Separate cells into apical and basal compartments The junction can be very selective and “leak-proof”, or be less selective Purpose: commonly regulates movement across membranes and other epithelial structures  Anchoring junction - desmosome Intracellular component: ▪ a plaque formed of molecules that are associated with cadherins ▪ Intermediate filaments (see cytoskeleton below) bind to the plaques Extracellular component: ▪ cadherins on one cell interact with cadherins on a neighboring cell Purpose – structural integrity for a wide range of cells and tissues Cadherins Anchoring junction – hemi-desmosome Similar to a desmosome, but extracellular component involves a protein known as an integrin ▪ Plaque still binds to an intermediate filament ▪ The integrin commonly binds to the basement membrane ▪ Usually how epithelial cells stay anchored to the basement membrane and underlying connective tissue Basal lamina Still associate intracellularly with intermediate filaments Integrins Anchoring junction – adherens junction These junctions also contain a plaque and may connect to: ▪ Another cell via _______ ▪ A basement membrane via ______ However, they connect with microfilaments rather than intermediate filaments The Cytoskeleton Performs the following functions: ▪ cellular movement cell can move through space (macrophage, fibroblast) or can change shape, performing work (muscle cells) ▪ organization of cellular components/organelles during mitosis and meiosis (interaction of DNA) shuttling of organelles and membrane-bound vesicles ▪ cellular structure strength (skin), shape (absorptive surfaces) ▪ communication intracellular signals that regulate growth, general function The Cytoskeleton - Review Cytoskeletal structures and functions: Microtubules Trafficking of organelles and cell division Organization of overall cellular structure Cellular movement Molecule – tubulin Microfilaments Cellular movement Structural organization of the plasma membrane Molecule - actin Intermediate filaments Overall structural integrity of the cell Variety of molecules – keratins, desmin Openstax – Anatomy and Physiology 2e, page 92, fig. 3.13 Features of the cytoskeleton Dynamic ▪ filament subunits (monomers, heterodimers) are constantly “building themselves” into their polymer strands Once monomers reach a critical concentration and interact with nucleating factors → polymer formation Tightly regulated ▪ filament assembly and disassembly is regulated by a huge array of intracellular signals ▪ govern structure and formation of polymers Can generate force ▪ many proteins interact with the strands of the cytoskeleton: move the cell or organelles along the axis of the strands generate power or motion in cells through contraction Microfilaments - Actin Monomer – G-actin; Polymer – F-actin ▪ Nucleating factors stimulate the formation of F-actin G-actin F-actin Microfilaments - Actin When F-actin is formed, it spontaneously degrades ▪ Each G-actin has an ATP bound Over time, the G-actin hydrolyzes ATP to ADP, which makes it more likely that it will “fall off” the F-actin strand The stability of F-actin depends on a number of factors, such as: ▪ Concentration of G-actin ▪ “caps” that can be applied to the F- actin that prevent disassembly ▪ Proteins that speed up or slow down the rate that G-actin hydrolyzes its ATP ▪ Nucleating factors or inhibitory factors that modify the formation of F-actin Microfilaments – actin in cellular structures Examples: A muscle cell: ▪ needs a stable, very organized system of parallel actin fibres ▪ generates lots of force ▪ Therefore actin filaments are “long-lasting”, very precisely organized, and strongly anchored to the cell membrane and other proteins A fibroblast: ▪ Needs to “crawl” to an area in order to deposit collagen/ECM ▪ Needs to “explore” its environment in order to find the right places to deposit collagen/ECM ▪ Therefore it organizes its actin filaments into meshes, fibres, and filopodium (kind of like feelers) under the cell membrane in order to accomplish these tasks  Microtubules More complicated than actin, but shares similar features: ▪ Protein monomer = tubulin Two types – alpha and beta – form dimers Alpha-beta dimers organize themselves in a helical tube ▪ Beta-tubulin also hydrolyze a nucleotide triphosphate For tubulin, they cleave GTP to GDP + Pi After GTP is cleaved, the dimer tends to “fall off” the microtubule and it falls apart ▪ Known as dynamic instability Harper’s Illustrated Biochemistry, 31 ed. Fig. 51-13 Microtubules Important for: Cellular organization – microtubules are formed from a microtubule organizing centre (MTOC) ▪ MTOC composed of two centrioles that form the centrosome Centrioles are also composed of microtubules, but have a unique shape – a tubulin triplet structure (9 tubulin triplets, known as the “9X3” structure) ▪ The MTOC and the microtubules that radiate from it form a cellular scaffolding that “moves” and “places” cellular structures at specific places in the cell helps determine polarity of the cell – i.e. if a cell has a side that faces a lumen and a side that faces a basement membrane Microtubules Important for: Cellular movement ▪ Cilia and flagella are formed from microtubules – these structures rotate and move in a whip-like fashion Flagella – present in sperm cells Cilia – present in the respiratory mucosa Cell division ▪ The MTOC splits and pulls chromosomes to new daughter cells using newly-generated microtubules Signaling – the primary cilium ▪ primary cilium found on most cells ▪ able to sense important stimuli in the extracellular environment to help with cellular localization or function Picture FYI – for visualization only Microfilaments, Microtubules, and Cellular Motors F-actin and microtubules form a network of dynamic filaments that “molecular motors” can move along, like a train moves along a track ▪ F-actin use myosin Myosin is a protein that can “walk” and advance along microfilaments ▪ Multiple different types of myosin exist ▪ In muscle, myosin movement along an actin scaffold causes the entire cell to contract Microfilaments, Microtubules, and Cellular Motors F-actin and microtubules form a network of dynamic filaments that “molecular motors” can move along, like a train moves along a track ▪ Microtubules use dyneins and kinesins They are proteins that can move along microtubules and cause the “whipping” movements of cilia and flagella Dyneins and kinesins move in opposite directions along microtubules  Intermediate filaments Many functions – most significantly providing stability to cells Much more diverse structure than actin & tubulin ▪ Long proteins with an alpha-helix conformation that coil around other monomers to form dimers ” Much more stable than actin or tubulin – do not hydrolyze GTP or ATP… so do not dissociate as readily ▪ However, they can change their structure in response to cellular needs Intermediate Filaments – some examples Type of intermediate filament Location Lamins A network of filaments just under the nuclear membrane Keratins Found in epithelial cells, hair, nails Strong, modified to limit water permeability Vimentin family Confer stability and structure to a variety of cells such as mesenchymal cells, muscle cells, glial cells Neurofilaments Intermediate filaments found in neurons