1_Membrane_structure_LEC_2024.pptx

Human Physiology Thou shall not pass… Except by special Membrane permission Structure Cell...

Human Physiology Thou shall not pass… Except by special Membrane permission Structure Cell membra ne 2024 Academic year 2025 avid L. Osborne, PhD. ofessor of Physiology  How do I teach! I use the “flipped” classroom model. What does that mean? Lectures are pre-recorded and class sessions are live in person: Lecture is recorded for you to watch any time before class. You should learn this material before coming to class. Class will NOT BE A LECTURE but will be a time to discuss this material and apply the knowledge learned ahead of time to answer questions or clinical scenarios. You will not be provided class slides (until after class), be prepared to This is done answer questions and participate in discussions. on purpose!!!!!!!!  Objectives 1. List and describe the roles of each of the major components of membranes: ions, phospholipids, sphingolipids, cholesterol, and protein. 2. Explain the role of proteins in membranes and compare peripheral versus integral membrane proteins. 3. Describe lipid anchors and major functions of proteins in membranes. 4. Explain the process of membrane fluidity and describe how it can be altered. 5. Describe the physical properties of membranes: dynamics, phases and Depiction of a Typical Cell and its Components Pay attention to the number of component s that are encased within Membra a membrane ne bound Guyton 14, fig 2-2 structure.  Membrane Bound Organelles Not list a complete Guyton 14th Fig 2-7 Guyton 14th Fig 2-9 Membranes separate compartments to allow different composition of contents. This difference in composition allows the existence of gradients. Gradients allow work to be done. Guyton 14 th Fig Guyton 14th Fig 2-4 2-5 Let's talk about Membrane Structure Basic Membrane Lipid components Structure There are three essential parts to a Parts of a Phospholipid phospholipid. Each individual part that can change may be different in various phospholipid molecules. The polar group is made up of a Polar attachment to the phosphate group and some phosphate group additional structure that imparts the hydrophilic nature of the molecule. This portion extends outward or inward to interact with Sugar backbone the watery environment. The sugar backbone holds the molecule together and imparts structural variety to the molecule. Fatty acid tails The fatty acid tail is the key (Non-Polar) hydrophobic component which May vary by number of allows the membrane to exclude carbons and the number water from passing through the of double bonds in the membrane. Structure of the tails fatty acid defines how the lipids lie in relation to each other and the degree of hydrophobicity Basic components As an What is different in Example, Parts of a Phospholipid this that can change molecule? The sugar (?) Polar attachment to the backbone is phosphate group different… An 18 Carbon Sphingosine is Sugar backbone the backbone instead of glycerol (3 carbons) Fatty acid tails notice tail is (Non-Polar) not connected May vary by number of by an ester carbons and the number bond (C=O) of double bonds in the This is fatty acid significant (Technicallyin neural an amino function. alcohol) The carbon-based group attached to the phosphate group can be replaced with any of these or many others What affect could this change have? In general, this changes the properties of the polar head group which may alter the function of the molecule ( We are not going to talk specifics here but that may be discussed at some point over the next two years) Marks 5, fig 10.3  How cholesterol fits into the membran Cholesterol and calcium can also be found in the membrane Ca++ Calcium is a divalent cation that can bridge polar head groups or interact with proteins in the membrane: Affects Permeability Comparison of a Phospholipid and Cholesterol Affects Fluidity What affect do you think this Thismay have? insertion will alter the fluidity of the membrane by disrupting the Marks 5, fig highly ordered lipid tails or stabilize 10.3  This rest of this session is about other components in the membrane and its properties and functions This is the basic structure in cartoon form: Notice… Lipid bilayer organization Basic structure of the way the lipids lie in the membrane to give it the bilayer … What do you think that means? Proteins in the membrane Similarities and differences between the inside versus Guyton 14th Fig outside of the 2-3 membrane  Physical Properties of Membranes Dynamic and flexible structures Can exist in various phases and undergo phase transitions Not permeable to large polar solutes and ions Permeable to small polar solutes and nonpolar compounds  Membrane Dynamics: Transverse DiffusionSpontaneous flips from one leaflet to Individual lipids undergo fast lateral another are rare because the diffusion within the leaflet. charged head group must transverse Motion of single phospholipid within the hydrophobic tail region of the the leaflet is very rapid, requiring no membrane. catalysis. If it occurs uncatalyzed, it is very slow  Enzyme Catalyzed Membrane Component Special enzymes— Diffusion flippases, floppases, and scramblases catalyze transverse diffusion Some flippases use energy of ATP to move lipids against the concentration gradient Three types of phospholipid translocators in the plasma membrane. PE is phosphatidylethanolamine; PS is phosphatidylserine Let’s investigate more components comprising a membrane and the properties they impart Recognitio n factors Interacts with ECF Limits polar molecule movement Interacts with ICF Peripher al Marks 5 fig protein 10-2  Proteins in the Plasma Membrane Integral Proteins: Span the entire membrane Have asymmetry like the membrane Tightly associated with membrane and removed by detergents that disrupt the membrane Integral proteins can move laterally in the membrane Peripheral Proteins: Associate with the polar head groups of membranes Relatively loosely associated with membrane Removed by disrupting ionic interactions either with high salt or change in pH Amphitropic proteins: Sometimes associated with membranes Loosely bound (discussed later in course) Six Types of Integral Membrane Proteins “This class of protein Can move laterally in the membrane” Integral membrane proteins. Types I and II have a single transmembrane helix; the amino-terminal domain is outside the cell in type I proteins and inside in type II. Type III proteins have multiple transmembrane helices in a single polypeptide. In type V proteins, transmembrane domains of several different polypeptides assemble to form a channel through the membrane. Type IV proteins are held to the bilayer primarily by covalently linked lipids, and type VI proteins have both transmembrane helices and lipid anchors.  Lipid Anchors Some membrane proteins are lipoproteins They contain a covalently linked lipid molecule – Long-chain fatty acids – Isoprenoids – Sterols – Glycosylated phosphatidylinositol (PGI) The lipid part can become part of the membrane The protein is now anchored to the membrane – reversible process – allows targeting of proteins – Some, such as GPI anchors are found only on the outer face of plasma membrane  Functions of Proteins in Membranes Receptors: detecting signals from outside – Light (opsin) – Hormones (insulin receptor) – Neurotransmitters (acetylcholine receptor) – Pheromones (taste and smell receptors) Channels, gates, pumps, and pores – Nutrients (maltoporin) – Ions (K-channel) – Neurotransmitters (serotonin reuptake  Cell membranes are anchored to the cytoskeleton of the cell There are also many molecules attached to these proteins that extend into the interstitial space outside the cell and perform many functions such as self identification/ incompatibility factors , receptors, (examples from red blood cells) transport, anchors Marks 5, fig and many other 10.5  Membrane Fluidity Temperature: The temperature at which membranes switch from a fluid to a rigid semi-crystalline state is called the transition temperature Too (Tm) Cold Temp >>> Tm = too fluid Temp > Tm = optimal fluidity Temp < Tm = rigid, semi-crystalline Just right Lipid Composition: Long chain fatty acids decrease fluidity Short chain fatty acids increase fluidity Saturated lipids = decreased fluidity Too Hot Unsaturated lipids = increased fluidity Cholesterol: Cholesterol in a fluid membrane = decreased fluidity Cholesterol in a rigid membrane = increased fluidity  Organisms can adjust the membrane composition Membrane fluidity is determined mainly by the fatty acid composition. More fluid membranes require shorter and more unsaturated fatty acids At higher temperatures cells need more saturated fatty acids – To maintain integrity At lower temperatures cells need more unsaturated fatty acids – To maintain fluidity  Membrane Fusion Membranes can fuse with each other without losing continuity Fusion can be spontaneous or protein- mediated Examples of protein-mediated fusion are: – Entry of influenza virus into the host cell – Release of neurotransmitters at nerve synapses  Summary of Membrane Structure Membranes are lipid bilayer structures that separate compartments. Structure varies by many factors that affect properties of the membrane. This separation allows gradients to be formed. Gradients are sources of “energy” Proteins in the membrane impart many functions Last point to remember the membrane due to these proteins is selectively permeable to some substances The End