6. Cell membranes

Schleiden and Schwann

• suggested a “barrier” between cells in 1839

• Matthias Schleiden - plants

• Theodor Schwan - animals 

Ernest Overton

• proposed that cell membranes are composed of lipids in 1895

• established that molecules enter cells based on their lipid solubility, leading to the "Overton Rule"

Irving Langmuir

• developed the Langmuir trough in 1917

• a laboratory apparatus used to study and manipulate thin films of molecules, called monolayers, on a liquid surface

Evert Gorter and François Grendel

worked with RBC (red blood cells) in 1925 to determine the structure in the cell membrane

    is it a monolayer or bilayer?

    a - surface area of RBCs (under calculated)

    b - extract the phospholipids (under calculated) 

    A: ZX = bilayer

• wBC's (white blood cells) have more cellular proteins

mudd + mudd (Stuart and Emily Mudd)

• described the surface composition of normal and sensitized blood cells

• Red Blood cells as oil

• White Blood cells as H₂O

Hugh Davson - James Danielli Model

• aka paucimolecular model

• proposed the model of the plasma membrane of a cell in 1935

• described the cell membrane as a "sandwich" model, with a central lipid bilayer (like the filling) sandwiched between two layers of protein (like the bread) 

  • protein - phospho-phospho-protein “sandwich”

JD Robertson

• proposed a modified version called the "Unit Membrane" model in 1957 based on new electron microscope studies

• described as was a single, uniform membrane structure instead (proven wrong)

Freeze Fracture (by Dan Branton)

• the “mosaic” nature of cell membrane

• technique used in electron microscopy to visualize the internal structure of biological samples, especially cell membranes

Cell Fusion

• heterolaryer - 2 nuclei 

• proteins are free to move laterally in the plane of the membrane 

• purpose:

  • preparation of hybridomas (monoclonal antibodies)

  • research on development, differentiation, and breeding (transplantation and replacement of nuclei)

  • research on regenerative medicine and cytotherapy

  • research on anti-cancer vaccination and cancer immuology

Cell Capping/protecting cell (patching)

• mAbs - 2 identical Fab regions

• same as cell fusion 

FRA (Fos-related antigen 1)

• a protein that is a component of the AP-1 transcription factor

• con A FRAP says that some proteins are fluid, some not

• binds to As proteins through their carbohydrates groups

• half of proteins are mobile and the other half not mobile 

Cytoskeleton and Extracellular Matrix

• limit lateral plasma membrane protein mobility

• extracellular - gives cell shape and mechanical resistance to deformation

• cytoskeleton - deforming the cell and the cell’s environment, and allowing cells to migrate

Mosaic Model

• propsed by Singer and Nicholson in 1972

• to describe the structure of the cell fluid-like, two-dimensional structure composed of a mosaic of phospholipids with embedded or attached proteins and carbohydrates, which can move laterally within the membrane

Red Blood Cells (RBCs)

benefits:

• plentiful and easy to get

  • pure cell population

  • few contaminating membranes 

  • few proteins 

  • right-side out and inside-out RBC vesicles

RBC Ghosts

• the membrane remnants of red blood cells that have lost their internal contents like hemoglobin

• formed in the body as a result of cell rupture (hemolysis) or in labs to be carriers

RBC membrane proteins

• vital for maintaining the cell's structure, function, and transport properties

• key proteins:

  • Band 3 and glycophorin - span the membrane,

  • cytoskeletal proteins like spectrin and ankyrin

  • band 4.1 - attached to the inner side of the membrane to provide structural support and flexibility

RBC membrane protein network

a complex system of integral and skeletal proteins that provides structural integrity, flexibility, and function to the cell

Elliptocytosis and Spherocytosis

• inherited red blood cell disorders that involve abnormalities in the cell membrane, but they differ in the shape of the red blood cells

• spherocytosis is characterized by spherical-shaped cells that are less flexible and have a decreased surface area, often leading to more severe hemolytic anemia

• Elliptocytosis involves oval or elliptical-shaped cells that are typically more mild, with many patients being asymptomatic

Vernon Ingram 

• the “father of molecular medicine”

• research on sickled cell anemia 

• found a single aminoacid substitution that caused sickle-cell anaemia

Phospholipid Bilayers

• consists of two layers of molecules with hydrophilic (water-loving) heads facing the watery environments inside and outside the cell

• while their hydrophobic (water-fearing) tails are oriented inward, creating a selective barrier

• protecting the cell and regulating the passage of substances to maintain a stable internal environment

Phospholipids

• hydrophilic (water-loving) phosphate "head" and two hydrophobic (water-fearing) fatty acid "tails

• dual nature, called amphipathic, allows them to spontaneously form a double-layered membrane in water, with the tails facing inward and the heads facing outward

• Synthesized on the
  Endoplasmic Reticulum (ER) with
  Flippase playing a critical role

LDL (low-density lipoprotein)

• Excess cholesterol causes
  Atherosclerosis

• Statins decrease LDL by
  inhibiting HMG-CoA reductase

Cell Membranes 

three possibilities of on how phospholipids and cholesterol move from ER to other organelle membranes:

1. Vesicular Transport (Vesicles)

2. Transfer at Membrane Contact Sites (Hypothetical Proteins)

3. Cytosolic Carrier Proteins (Binding Protein)

MinION

sequencing device that uses a highly stable, engineered membrane protein (alpha -hemolysin) inserted into a synthetic membrane to act as a nanoscale sensor that identifies the sequence of DNA bases by measuring the subtle, characteristic electrical current changes each base produces as it passes through the pore

Sodium potassium pump

• Uniport, Symport and Na+/K+ Pump (ATPase) working together

• critical for quick
  rehydration in cases with Cholera Toxin

Cell Membrane Proteins

• discovery of Flippase that is required for fluorescent probes

• channels - fastest:

  • non gated

  • ligand  - gated

  • vintage-gated

• transporters - no ATP required

• cholera toxin:

  • drink Na+ and Glucose  

  • quick to rehydrate 

Hydropathy Plots

• explain multipass nature of integral
  membrane proteins

• scores each amino acids based on its hydrophobicity

Membrane Specializations

• differentiated structures of the plasma membrane that allow a cell to perform specific functions

• includes:

  • Microporous membranes and kidney cells

  • Adherens

Adhere Junctions

• F-acting is critical (E-cadherin - Ca⁺²)

• encircles the cells in the apical region

• in NaCa⁺² no E-cadherin function

• does:

  • cell adhesion

  • cis-configuration

  • trans-configuration

Desmosomes

• cell adhesion “spot welds”

• skin (epidermis) like Hemidesmosomes

• cadherins

ex: Pemphigus -an autoimmune disorder that attack __ in humans and canines 

Tight Junction 

• kidney intestinal

• epithelial cells of the bladder

• separate liquid

• sodium Fluorescein leakage assay 9an in vitro test that measures how a substance affects the permeability of an epithelial cell layer by using sodium fluorescein dye)

• lanthanum hydroxide 

Gap Junctions

• aka electrical junction

• allows communication between cells 

• allows small molecules or ions can pass through

Neurochemical/(mixed) Synapses

using chemical messengers (neurotransmitters) to send signals across a gap called the synaptic cleft