Membrane Structure and Function

Introduction to Membrane Structure and Function

  • Water dictates the alignment of hydrophobic compounds, such as lipids, leading to the spontaneous formation of membrane structures

    • creates boundary

      • 1) The importance of membranes to biological life.

      • 2) The properties of membranes that allow them to enhance survival

      • 3) The composition of membranes.

      • 4) The functions that occur at the site of membranes.

Reasons for Having Membranes: Organizational and Protective Functions

  • Membranes serve as a mechanism for organization, allowing the cell to maintain order and work efficiently.

    • maintaining life is tenuous, often ATP is the energy demand, combating entropy to organize membranes into micels

  • Membranes facilitate compartmentalization, which allows specific processes to be isolated from the rest of the cell environment

    • internal membranes divide processes and improve efficiency

  • Barrier to diffusion to larger and/or more polar molecules thus decreasing energy demand and increases chance of survival

    • Mitochondrial Function: Internal membranes in the mitochondria isolate the electron transport chain, passage of electrons is highly efficient

      • pathways for glucose are localized to cytosol while TCA and Krebs are in mitochondria

      • enzymes for fatty acid synthesis (cytosol) are separated from fatty acid catabolism (beta ox) by the inner mitochondrial membrane

  • The Nuclear Envelope: This structure separates genomic DNA and the critical processes of replication and transcription

  • Signal Transduction: of hydrophilic signals (such as polypeptide hormones or neurotransmitters) interact primarily with proteins linked to the cell membrane.

  • Intracellular Transport: maintains the unique chemical and protein environments of individual intracellular compartments

  • Membranes allow for biological adaptation because their composition can change

  • The ability to alter membrane composition ensures that the cell can maintain homeostasis despite external stressors or changes.

What properties of membrane enhance the chance of survival?

  • Flexibility: components such as lipid bilayer, proteins, glycoproteins, and glycolipids behave as individual units NOT covalently bound to each other → fluid mosaic model

    • allowing shifting in position

    • and van der Waals bonds promote adherence of neighboring lipids creating consistency of olive oil

    • Allows for movement of the cell: can change position or shape wile membranes maintain compartmentalization

    • Allows for growth: allows exocytosis and endocytosis

      • e.g. cell growth, synaptic vesicle recycling, neurotransmitter and hormone release, nerve regeneration, insulin regulation of glucose transporters

      • Exocytosis: Hydrophilic signal store in cell and released when given appropriate stimulus

        • polypeptide hormones and most neurotransmitters

      • Endocytosis: The process of removing membrane, often associated with the uptake of materials (e.g., clathrin-coated pits).

  • Membranes are self healing

    • recombine and form intact barrier after small tears increases survival

    • self-seal allows for cell division

    • allows exocytosis

      • expansion on total cell membrane surface area

      • incorporates new protein into membranes and regulates transport and signal sensitivity (membrane remodeling)

  • Steps to exocytosis:

    • vesicles await signal for exocytosis (action potential or Ach, binding to ligand)

    • cascade

      • 1. increase intracellular Ca

      • SNARE + SNAP interaction

      • hydrolyze ATP

      • vesicle drawn to cell membrane the outer leaflet of the vesicle fuse with inner leaflet of cell membrane

      • inner leaflet of vesicle fuse with outer leaflet of cell membrane

      • results in interior of vesicle being contiguous with extracellular fluid

  • Endocytosis

    • portions of membrane removed to form intracellular vesicles (occurs in eukaryotic cells and osteoclasts)

    • can occur to remove proteins from cell membrane (glucose transporters: GLUT 1, 2, 3, 4)

      • synaptic vesicle recycling

    • all examples of pinocytosis where the intravesicular content is simply extracellular fluid

      • NOT REGULATED

    • or phagocytosis: incorporate particulate matter form extracellular fluid

    • involved in disease process. -hepatitis, poliomyelitis, AIDS, and iron toxicity

  • Steps of Endocytosis: inner leaflet of endocytotic vesicle is comprised of the outer leaflet. of the cell membrane

    • Receptor mediated endocytosis is regulated

      • assembly of clathrin at location of invagination

      • initial invagination is called a coated pit → includes occupied receptors pinches off and forms a coated vesicle

      • then coated vesicle fuses with primary lysosomes to form secondary lysosome (digest contents to yield amino acids, simple sugars and nucleotides

      • endocytosis requires energy (often ATP hydrolysis), Ca in extracellular fluid and contractile elements of microfibrils in cell

Membranes are selectively permeable

  • lipid bilayer creates a hydrophobic internal core; consequently, hydrophilic compound which begins to diffuse goes to higher energy state as it “sheds” hydration sphere (coating of water molecules around ion or molecule that stabilize hydrophilic compounds

  • Ability of compounds to cross the membrane adjusted by proteins as transporters (facilitated diffusion or active transport) including channels (voltage gated or ligand gated)

    • saturable kinetics (Transport maximum Tmax) says there is only an x amount of molecules that may pass, this does NOT apply to ion channels

      • bc there is a finite number of transport molecules

    • Ion channels flow freely, no substrate contact

  • membranes keep undesirable compounds out and trap desired inside

    • we need glucose for energy thus we have glucose transporters, necessary for survival

      • insulin dependent and not

    • acquired glucose phosphorylated by hexokinase → glucose 6 phosphate (more hydrophilic than glucose

    • G6P is NOT substrate for GLUT transporter and reduces chance glucose transported out of cell

Composition of membranes

  • Lipids

    • barrier to diffusion and anchor proteins

    • passive function

  • proteins

    • active functions: receptors, transporters, effectors, energy production and physical linking sites

  • sugars

    • serve as recognition

    • cell surface receptors, components of ECM, like cells (tissue formation), foreign materials (immune)

    • present as glycoproteins and glycolipids

  • membrane turnover - changes over time

    • through exocytosis and endocytosis

    • composition of leaflets DIFFER

      • flip-flop: lipid can move from inner to out leaflet or vice versa

Functions at membranes:

  • Transport:

    • simple diffusions does not require membrane proteins but facilitated diffusion, active transport, endocytosis and exocytosis all require prot.

  • Receptors

    • present in target cells of hydrophilic signals.

    • Hydrophilic signals include most neurotransmitters, most autocrines and paracrines, and polypeptide hormones.

    • Binding of the signal to the cell surface receptor is just the beginning of a cascade of events that often involve GTP-binding proteins, effectors and the eventual generation of one or more second messengers

  • Pumps

    • form of transport

    • most common active transport

      • primary active transport: ATP directly hydrolyzed to provide energy in transporting the molecule

        • e.g. Na/K ATPase; sodium/potassium pump

    • secondary active transport: direct source for the active transport is the electrochemical gradient of an ion, commonly sodium glucose transporter, or hydrogen ion transporter, or neurotransmitter reuptake

Transporters and channels:

  • both proteins assist in movement of chemicals across membranes:

    • channels are proteins that allow ions down electrochemical gradient like facilitated diffusion

      • allow higher rates of flux (unidirectional net flow)

      • Channels do NOT exhibit saturable kinetics

Facilitated Transporters

  • HCO3-/Cl- Exchanger in Red Blood Cells

  • GLUT1 glucose transporter (found in Red Blood Cells and many other cells

  • There are at least 12 glucose transporters that   have been identified (GLUT1 – GLUT12):

    • GLUT1 – Ubiquitous

    • GLUT2 – Liver, Pancreatic Islets, Intestine

    • GLUT3 – Brain/Neurons

    • ****** Insulin-dependent  GLUT4 – Muscle, Fat, Heart

Active transporters:

  • Na/K ATPase (an ELECTROGENIC ANTIPORTER)

  • SERCA pump (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase – ELECTROGENIC UNIPORTER)

  • ATP Synthase (Inner mitochondrial membrane)

  • ABC Transporter (ATP-Binding Cassette – Pumps for amino    acids, peptides, lipids, bile salts and others)

  • Intestinal and Renal Glucose Pumps (Sodium-Dependent)

  • Intestinal and Renal Amino Acid Pumps (Sodium-Dependent)

  • Calcium Pumps in many cells (Sodium-Dependent)

    • Each sodium-dependent pump above is an example of SECONDARY ACTIVE TRANSPORT, while ATPases are PRIMARY ACTIVE TRANSPORT.

Channels:

  • Voltage-gated Sodium and Potassium Channels (produce AP in excitable cells like neurons and muscle)

  • Ligand-gated Na+/K+ Channel (part of Nicotinic Cholinergic Receptors, produces the End Plate Potential in skeletal muscle cells)

  • MANY Ligand-gated channels for neurotransmitters.

  • Aquaporins (water channels)

    • AQP1 and AQP2 are in collecting duct cells of the kidney.

    • Aquaporins allow water to pass across membranes even more easily than if there were no channel present.

Component of Membranes

  • lipids, proteins, and glycolipid, glycoprotein (sugar, oligosacarides)

    • sugars are usually chains attached to lipid and protein

  • Leaflets:

    • Outer Leaflet: This layer is characterized by its lipids having polar heads oriented toward the extracellular fluid.

    • Inner Leaflet: This layer is defined by lipid polar heads oriented toward the intracellular fluid.

      • Amphipathic: both hydrophilic (water-loving) region and a hydrophobic (water-fearing) region on the same molecule

How is membrane held together?

  • Universe prefers to be at lowest possible energy state

    • polar heads to aqueous environment (hydrogen bond and electrostatic bond) and fatty acid tails away from water (Van der Waals between fatty acid chains and glycolipid)

      • increase bonding is possible if fatty acids are longer and no kinks in chain - otherwise water can fit through gap and destabilize

Membrane fluidity:

  • variable fluidity increases chance for survival

  • Increase in membrane fluidity

    • short length fatty acid chains

    • increased presence of unsaturated fatty acids

    • decreased cholesterol content of membranestructures.

Lipid Composition and Cholesterol

Cholesterol and Fluidity:

  • Cholesterol acts as a fluidity buffer within the membrane.

  • The ring structure of cholesterol can act to block the movement of other lipids, contributing to the overall stability or rigidity depending on the temperature.

Lipids:

  • phospholipids

  • glycolipids

  • cholesterol

Fatty acids are long chains of hydrogenated carbons ending with carboxyl group

number of carbons

Name

Saturated: Unsaturated

16

Palmitic

Palmitoleic (16:1)

18

Stearic

Oleic (18:1)

Linoleic (18:2)

Linolenic (18:3)

20

Arachidic

Arachidonic (20:4)

  • Chemical Signaling Precursors:

    • The membrane contains lipid components that serve as precursors to important signaling molecules like prostaglandins.

Variability in Membranes

  • lipid, protein, and sugars vary in amounts

  • those involved with recognition tend to have more protein in membrane

  • if you see sugar in membranes → recognition

    • mostly found in outer leaflet also found in luminal, the polysaccharide layer they form is known as the glycocalyx

  • glycoproteins: primarily outer leaflet, is an oligosaccharide attached to protein

    • cell-cell recognition, form linkages between cell and ECM and other cells in recognition and absorption

    • transmembranous glycoprotein - Integrins

      • extracellular portion of integrin bind fibronectin (another glycoprotein ) and fibronectin attaches to ECM

      • intracellular attach to cytoskeleton providing direct physical link between elements within and outside the cell

        • explains how tissues are held together and take same orientation in space