BIOL1040 Cell Membranes

monchkin

Fluid mosaic model

Cell membrane is fluid with a mosaic of proteins embedded in it

Evidence for fluid mosaic

Dyed membranes of mouse and human proteins different colours

fused cells and examined proteins after an hour

result - proteins mixed, showing there is lateral movement

Movement of phospholipids in membrane

continuous lateral movement (10^7 times a second)

• means embedded proteins can move around

flip flop (~once a month)

What affects membrane fluidity?

Unsaturated hydrocarbon tails

• form kinks in tails, making them more rigid

• can’t pack as closely together

• more fluid membrane

Saturated tails

• pack closely together as tails flexible

• more viscous membrane

Cholesterol

• acts as temperature buffer

• high temp = more fluid, cholesterol acts to decrease fluidity

• low temp = more viscous, cholesterol acts to decrease viscosity

Integral membrane proteins functions

• transport

• enzymatic activity

• signal transduction

  • receptor for ligand to bind to

• cell-cell recognition

• cell-cell attachment/ intracellular joining

  • used to make tissues

• attach to cytoskeleton and ECM

Osmosis

Diffusion of water through selectively permeable membrane into another aqueous compartment containing a non-permeable solute at a higher concentration

Osmotica

Solutes that are osmotically active

• won’t pass through membrane, exert osmotic pressure which drives movement of water to balance out this solute concentration

Osmotic pressure

Force that causes water to move to negate a concentration gradient

Facilitated Diffusion

Passive transport sped up by integral membrane proteins

Types of integral membrane proteins used in facilitated diffusion

Carrier/Transporter

Channel

Channel protein and examples

Provides channel for hydrophilic particles such as ions to travel down concentration gradient

no work required (no ATP)

examples

• aquaporins - for water

• ion channels - open and close in response to stimulus (gated)

Carrier/transporter protein 

solute binds to protein in extracellular open configuration, changing conformation to intracellular open allowing solute to enter cell

e.g., glucose, amino acid transporters

Active transport

goes against concentration gradient, requires ATP

mediated by transporters, not channels since channels would just let the solute back down concentration gradient

Electrogenic pump

creates voltage across membranes by moving ions

• sodium/potassium ATPase

• proton pump

Cotransport

active transport of one solute indirectly drives another

e.g., proton gradient from proton pump drives sucrose H+ cotransporter in plants, sodium potassium ATPase cotransports glucose in animals

Endocytosis types

pinocytosis - cell drinking

phagocytosis - cell engulfing large particles or other cells

receptor mediated endocytosis - solute binds receptor, cell endocytoses bound receptors

Paracrine signalling

local - chemical molecules sent btwn cells

Autocrine signalling

local - cell secretes chemical that signals itself

Synaptic signalling

local - nerve cell releases neurotransmitters that innervate another nerve or muscle/other cell

Endocrine signalling

long distance - hormones travel through body fluid to trigger responses in specific target cells

Neuroendocrine signalling

long distance - neurosecretory cell secretes neurohormones which travel through body fluid to trigger responses in target cells

Stages of cell signallng

Reception

• ligand bind to receptor

  • cell surface if hydrophilic

  • inside cell if hydrophobic

Transduction

• convert to different energy or messenger within cell

• amplification of signal

Response

Receptor families (list, 2 families, 3 receptors in the first, 1 in the second)

Plasma membrane receptors

• G-protein coupled receptors

• Ion channel receptors

• Receptor tyrosine kinases

Intracellular receptors

• Steroid receptors

Ion channel receptors

ligand gated ion channel

ion channel opened by ligand

fast - good for neurotransmission

GPCR

Largest family of receptors

7 transmembrane spanning regions

Activated by variety of stimuli

GPCR coupled to heterotrimeric (3 parts) G protein

Signal amplification

Process

• first messenger binds to GPCR, activates

• GPCR binds to G protein, bound by GTP which activates it

• G protein binds to adenylyl cyclase, GTP hydrolysed, activating adenylyl cyclase

• activates second messenger (e.g., cAMP) leading to cellular response 

Receptor Tyrosine Kinases

Reception - RTKs dimerise on membrane, binding (active)

Transduction - phosphorylation cascade amplifies signal, mediated by kinases (enzymes that phosphorylate)

Response - several at once

Used for metabolism, cell growth, cell reproductio

Role of protein phosphorylation

• conformational change

• different binding

• protein may move to different location

Steroid Receptors

receive hormones intracellularly

slower response

can act as transcription factors by binding DNA to nucleus

Cortical rotation

Plasma membrane and cortex (region just below membrane) rotate relative to inner cytoplasm

point of sperm entry becomes animal pole (smaller cells

Cleavage

Rapid cell division via mitosis

only M and S phase

stage ends when not enough cytoplasm to divide - too little RNA to meet protein needs of cell

results in morula (ball of cells)

Types of cleavage

Complete - holoblastic division

• if less yolk (e.g, sea urchin)

  • equal cleavages

  • blastomeres of similar size

• if yolk only in specific region (e.g., frogs)

  • cleavages unequal

  • cells in yolky region (vegetal pole) chunkier

Incomplete - meroblastic division

• if a lot of yolk (e.g., chickens)

  • cleavage furrow slowed or blocked by yolk

  • complete divisions restricted to less yolky areas

  • Flat disk of incompletely cleaved cells on top of yolk

Blastulation

morula rearrangement into blastula

• inner layer = embryoblast

• outer layer = trophoblast

  • provides nutrient to embryo

  • form placenta

• hollow cavity = blastocoel

implantation

• trophoblast secretes enzymes that digest endometrium, allowing implantation

post implantation

• trophoblast expands forming placenta

• 4 extraembryonic membranes

  • amnion

    • encloses developing embryo

    • contains amniotic fluid to provide moist environment 

  • 3 other membranes

Gastrulation

reorganisation of blastula into 3 distinct layers

• ectoderm

  • outer layer, covers embryo

  • forms outer layer of skin

  • forms nervous system from neural plate

• mesoderm

  • middle layer

  • forms muscle, skeleton and connective tissue

• endoderm

  • innermost layer

  • lines digestive tract

  • forms internal ducts and organs such as liver, pancreas and lungs

formation of archenteron

• primary digestive tube formed by invagination

organogenesis

Cells differentiate into organs

• neurulation, formation of nervous system is first

• heart is one of first organs to form

• muscles from somites

• limbs form from limb buds

Organ differentiation - fate mapping

• where cells need to be and what they end up being is preprogrammed

  • dictated by gene expression and protein signaling

• determination

  • establishes a cell/group of cell’s fate

• differentiation

  • process of specialisation in structure and function

• bilateral symmetry

  • left/right axis symmetrical

  • head/tail axis asymmetric

    • melanin fills animal hemisphere

    • yolk fills vegetal hemisphere (more nutrients)

    • hemispheres determined by cortical rotation

Neurulation

• formation of nervous system

• process

  • some mesoderm cells form notochord

    • rod that extends along dorsal side of embryo

    • eventually forms spinal cord

  • signal from notochord causes inward folding of ectoderm at neural plate (area above notochord)

  • ends of neural plate fuse and disconnect to form autonomous neural tube

limb formation

cells in limb buds release inductive signals (proteins) to themselves and each other

combined with gene expression this determines

• spatial orientation

• arrangement of organs and tissues

the limb bud determines the formation of a limb, if limb bud was transplanted somewhere else that limb would still grow

Frog embryo developmental comparison

gastrulation - cells move quickly

less developed when hatched as tadpole bc tadpole further develops into frog

Chick embryo developmental comparison

cleavage

• incomplete due to yolk (meroblastic division)

gastrulation

• blastula is flat disk

• cells migrate to middle of disk to form primitive streak

• cells at primitive streak migrate downwards to form 3 layers

• neural groove forms where primitive streak is, gets deeper to form neural tube (spinal cord)

clearly defined organs and limbs at end of development

Hormones during embryo development (trimesters and labour)

1st trimester

• human chorionic gonadotropin (hCG) secreted

  • acts like LH from the pituitary

  • maintains corpus luteum (progesterone and oestradiol secretion)

2nd trimester

• hormone level stablise

  • hCG secretion declines

  • corpus luteum deteriorates

• placenta completely takes over production of progesterone

Labour

• 2 hormones

  • oestradiol

    • from ovaries

    • activates oxytocin receptors on uterus

    • helps oxytocin bind to uterus wall to cause contractions

  • oxytocin

    • from foetus’ and mother’s posterior pituitary

    • stimulates contraction of uterus

    • stimulates placenta to make prostaglandins to stimulate more contractions

    • positive feedback loop

Placenta (purpose, blood flow, material exchange mechanisms)

inside endometrium

purpose

• exchange gases, nutrients, waste btwn foetus and mother

maternal blood

• through arteries into maternal blood pools in endometrium, out through veins

foetal blood

• stays in vessels

• through arteries to capillary beds in maternal blood pools, out through veins

material exchange

• diffusion

• activate transport

• selective absorption (things like glucose) btwn foetal capillary bed and maternal blood pools

When do we use contraception?

any time before implantation

Methods for detecting pregnancy disorders

ultrasound imaging

• analyse baby size, organ development, blood flow

amniocentesis (amniotic fluid) and chorionic villus (tissue) sampling

• sample cells with needle

• conduct PCR

PCR on maternal or foetal blood

Describe the process of in vitro fertilisation

Combining oocyte and sperm in lab

incubate until undergone cleavage (at least 8 cell)

implantation in uterus

In vitro fertilisation - when might we inject whole sperm or nuclei directly into oocyte

if mature sperm defective/low in number