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KAZAKH NATIONAL MEDICAL UNIVERSITY

NAMED AFTER S.D. ASFENDIYAROV

COURSE OF BIOPHYSICS

Medical physics

Lecturer Nursultan Japashov

Almaty 2021
Lecture №1

Studying the structure and functions


of biological membranes on the model
of an electric capacitor.
• The cell - elementary structural and functional
unit of the structure and functioning of all
organisms (except for viruses), which has its
own metabolism, capable of independent
existence, reproduce (animals, plants and
fungi)
Types of cells
Plasma membrane
• The plasma membrane or plasmalemma, - the
most constant, the basic, universal for all cell
membranes. It is the thinnest (about 10 nm)
film covering the entire cell.
• Plasmalemma consists of protein molecules
and phospholipids.
• An important part of the cells are biological
membranes.
• They separated the cell from the environment,
• protect it from harmful external influences,
• manage the exchange of substances between the
cell and its environment,
• contribute to the generation of electrical
potentials,
• are involved in the synthesis ATP energy in the
mitochondria, etc.
• Essentially, membranes forming the cell
structure and perform its function.
Membranes have high fastness, stability, pliability and
also electrical insulating properties.
All membranes in their organization and structure exhibit
a number of common characteristics.

They:
• consist of lipids, proteins and
carbohydrates;
• They are flat closed structure;
• have an inner and an outer
surface;
• selectively permeable.
• phospholipid molecules are arranged in two rows - hydrophobic
ends inward, the hydrophilic heads towards the internal and
external aqueous medium.

• In some places bilayer (bilayer) of phospholipids thoroughly


permeated with protein molecules (integral proteins). Inside
these channels are protein molecules - the pores, through which
pass the water-soluble substance.

• Other protein molecules penetrate the lipid bilayer of the one


half or the other surface of the eukaryotic cells are peripheral
membrane proteins.

• Molecules of lipids and proteins held through hydrophilic-


hydrophobic interaction.
• A liposome is a spherical vesicle having at least one 
lipid bilayer.
• The liposome can be used as a vehicle for administration
 of nutrients and pharmaceutical drugs. 
• Liposomes can be prepared by disrupting biological
membranes (such as by sonication).
• All cell membranes are fluid moving structure,
since the molecule of lipids and proteins are not
linked by covalent bonds and are able to move
fast enough in the plane of the membrane. This
membrane can alter its configuration, ie. have
fluidity.

• Membranes - structure is very dynamic. They


quickly restored after the damage, as well as
stretch and shrink with the cell movements.
• Although the lipid bilayer
structure itself is stable, the
individual phospholipid and
sterol molecules have great
freedom of motion within the
plane of the membrane. They
diffuse laterally so fast that an
individual lipid molecule can
circumnavigate an erythrocyte
in a few seconds.

• "flip-flop" diffusion it is the


movement of molecules from
one face of the bilayer to the
other.
The physical properties of the membranes

• The density of the lipid bilayer is 800 kg / m3,


which is lower than that of water.

• Dimensions. By electron microscopy data,


membrane thickness (L) ranging from 4 to 13
nm, and various cell membranes characterized
by different thickness.

• Viscosity. The lipid layer of the membrane has a


viscosity η = 30-100 mPa*s (corresponding to
the viscosity of vegetable oil).
The physical properties of the membranes

• Membrane - a capacitor. Double-layer phospholipid


membrane likens flat capacitor whose plates are formed
electrolytes extracellular and intracellular (cytoplasmic)
solutions with them immersed in surface proteins and
heads of lipid molecules. The covers are separated by a
dielectric layer formed by the nonpolar part of the lipid
molecules - double layer of their tails. Electric capacity
of 1 cm2 of the membrane is 0.5-1.3 microfarads.

• The dielectric constant of the membrane is:


for phospholipid field ε = 2,0-2,2;
for the hydrophilic region ε = 10-20.
Models:
• The first model of the structure of biological membranes was proposed in
1902. Overton noted that the membranes are best permeant, are composed
of a thin layer of phospholipids.
• In 1925 Gorter and Grendel that the lipids in the membrane are arranged
in a bimolecular layer.
• Model Danielli and Devson, 1935, "sandwich" model. According to this
model, the membrane - trilayer: it is constituted by two spaced edges of the
layers of protein molecules to the lipid bilayer in the middle; It formed a
kind of sandwich - lipids, such as oil, between the two "slices" of the
protein.
• Liquid-mosaic model of the membrane is now generally accepted.
However, like any model, it gives a rather simplified and schematic picture
of the structure of the membrane. In particular, it was found that protein
"icebergs" does not always float freely in the lipid sea, and can be
"anchored" on the inner (cytoplasmic) cell structure. These structures
include the microfilaments and microtubules.
Liquid-mosaic model of the membrane
Properties:
• The membrane is selectively permeable and able to
regulate what enters and exits the cell, thus
facilitating the transport of materials needed for
survival. The movement of substances across the
membrane can be either "passive", occurring without
the input of cellular energy, or active, requiring the
cell to expend energy in transporting it.
• The membrane also maintains the cell potential.
• The cell membrane thus works as a selective filter
that allows only certain things to come inside or go
outside the cell.
Options:
• barrier - provides an adjustable, selective, passive and
active metabolism with the environment.
• selective permeability means that the permeability of the
membrane to the different atoms or molecules depends on
their size, electric charge, chemical properties.
• transport - through the membrane occurs transport of
substances into the cell and out of the cell. Transport
through the membrane provides for: the delivery of
nutrients, removal of end-products of metabolism.
• Matrix - provides a certain relative position and orientation
of membrane proteins and their optimum interaction.
• Manual - provides autonomous cell, its intracellular
structures, and a connection to other cells (in tissue).
Formulas
• The membrane in its structure resembles a flat capacitor plate are
formed by surface proteins, and the role of the dielectric performs
lipid bilayer. Using the formula for the parallel plate capacitor can be
estimated with a dielectric constant of the hydrophobic and
hydrophilic regions of the membrane, knowing the limits of variation
of the thickness of the membrane.

C=
• where: ε - dielectric permeability,
• F/m (Farads per metre) - electric constant
• s- area,
• d-distance between plates
Frequency hopping molecules due
to lateral diffusion equal

ν=
where
D - coefficient of lateral diffusion;
A - area occupied by a molecule on the surface of the
membrane.
• Time settled life of the
molecule in the same
position is inversely
proportional to frequency
hopping

• = • the mean square


displacement of
molecules in a time t is

• S=2
Biophysical methods

• Biophysical methods are techniques to study the


structure, properties, dynamics or function of
biomolecules at an atomic or molecular level.
• They encompass a range of techniques including
• microscopy,
• spectroscopy,
• electrophysiology,
• single-molecule methods
• molecular modelling.
Atomic force microscopy

• Atomic force microscopy (AFM), a form of


scanning probe microscopy, is a technique
where a cantilever with a sharp tip is
systematically scanned across a sample
(biological or material) surface to produce a
nanometre-resolution topographic map. AFM
can also be used to measure forces between
the tip and sample.
Transport of substances
through membrane
• In cellular biology, membrane transport refers to
the collection of mechanisms that regulate the
passage of solutes such as ions and small molecules
 through biological membranes, which are lipid
bilayers  that contain proteins embedded in them.
• The regulation of passage through the membrane is
due to selective membrane permeability - a
characteristic of biological membranes which allows
them to separate substances of distinct chemical
nature. In other words, they can be permeable to
certain substances but not to others.
• Thermodynamically the flow of substances
from one compartment to another can
occur in the direction of a concentration or 
electrochemical gradient or against it.
• If the exchange of substances occurs in the
direction of the gradient, that is, in the
direction of decreasing potential, there is no
requirement for an input of energy from
outside the system;
• if, however, the transport is against the
gradient, it will require the input of energy,
metabolic energy in this case.
What is transport of substances?
• Membrane transport -
transport of substances
through the cell
membrane into the cell
or cells, carried out
through a variety of
mechanisms - simple
diffusion, facilitated
diffusion and active
transport.
Transfer phenomena
• Spatial transfer of the mass, impulse, energy, electrical charges
and other physical quantities are referred to the transfer
phenomena.

• Significant for the biological membranes transfer phenomenon


is the transfer of substance and charge.

• In biophysics the term “transport of particles” is usually used.

• Transport of substances through the cell membranes has great


importance for medicine and biology because the reasons of
many diseases and also the action of medicaments can be
explained by the violations of the systems of active and passive
transport.
Passive transfer may be due to different gradients. Such
gradients can be:

1. Concentration gradient transfer conditioning


substance at a concentration difference in the cell and
the surrounding fluid.
2. The osmotic gradient that occurs when a difference
in osmotic or, more important for biological systems,
the osmotic pressure within and outside the cell.
3. Diaphragm gradient arising in the presence of a
semipermeable membrane, a well-transmissive low-
molecular ions and bad - high molecular weight.
• 4. Gradient solubility occurring at the boundary
between two immiscible phases, if the substance has
uneven solubility in these phases.
• 5. The electrochemical gradient due to difference
of electrochemical potentials. Movement of ions
down an electrochemical gradient can occur in the
case when they move against the concentration
gradient or electrical potential gradient against,
since the gradient is the sum of the electrochemical
potential of chemical and electrical effects.
Mechanisms of passive transport
The four main kinds of passive transport are
• diffusion (osmosis),
• facilitated diffusion,
• filtration.
Simple diffusion
• simple diffusion is the random movement of
particles (molecules) from a region of high
concentration to a region of low
concentration.
• this process will continue until a dynamic
equilibrium reached.
• example - diffusion of oxygen from the alveoli
into the adjacent blood capillaries.
Facilitated diffusion
• facilitated diffusion is the passive movement
of molecules or ions down a concentration
gradient.
• the process involves special pore
proteins (channel proteins) or specific carrier
proteins in the plasma membrane.
• Example - the reabsorption of glucose and
amino acid from the villi into the blood
capillaries.
• the particular molecules
combine with the specific
active site of the carrier
protein.
• The carrier protein
changes its shape to allow
the molecules to pass
through to the other side
of the plasma membrane.
• After assisting the
movement of molecules
to the other side of the
plasma membrane, it is
free to bind with other
molecules.
Osmosis
• is the random movement of water
molecules from a region of high
concentration of water molecules to a region
of low concentration of water molecules
through a partially permeable membrane.
• Example - the reabsorption of water molecules
from the nephrons into the blood capillaries.
Filtration
• Filtration is the process by which water soluble drug of relatively low
molecular weight crosses the plasma membrane through pores as a
result of hydrodynamic pressure gradient across the membrane.

• The glomerular membrane of the kidney is a good example of a filtering membrane. Glomerulus
can be considered as filter placed in the funnel. Bowman’s capsule can be compared as funnel.

The rate of filtration is dependent on:

• The extent of concentration gradient,


• Filtering force,
• The size of the drug molecule relative to the size of the pore through which it is to be
filtered.

• Certain substances with high molecular weight (e.g. proteins) appear to be filtered
through intercellular channels rather than through the pores of the plasma membrane.
Filtration
Summary
Fick's law
• The diffusion rate is determined by Fick's law

J= - D

J = - DK
where: j - flow of substances,
l - the thickness of the membrane
The permeability coefficient

Where:
P- permeability
P= coefficient
D-coefficient of diffusion
K- coefficient of distribution
l- the thickness of the
membrane
• Transport of ions through the lipid layer via simple
diffusion takes place very slowly. According to Born's
formula, for the penetration of ions of one mole of a
solution with 𝞮=80 dielectric permittivity
membrane 𝞮=2 must overcome the potential barrier
of equal:

W 
ze 
2
NA  1

1 
 
8 0 r M B 

where: z-ion charge in units of the elementary charge;


NA - Avogadro's number;
 - dielectric constant;
r- ion radius.
• Tonicity is a measure of the effective osmotic pressure
 gradient, as defined by the water potential of two solutions
 separated by a semipermeable membrane. In other words,
tonicity is the relative concentration of solutions that
determine the direction and extent of diffusion.
• It is commonly used when describing the response of cells
 immersed in an external solution.
• Unlike osmotic pressure, tonicity is influenced only by 
solutes that cannot cross the membrane, as only these exert
an effective osmotic pressure.
• Solutes able to freely cross the membrane do not affect
tonicity because they will always be in equal concentrations
on both sides of the membrane.
• It is also a factor affecting imbibition.
There are three classifications of tonicity that
one solution can have relative to another.

The three are hypertonic, hypotonic, and isotonic


• There are three types of solutions that can occur
in your body based on solute concentration:
 isotonic, hypotonic, and hypertonic.
• An isotonic solution is one in which the
concentration of solutes is the same both inside
and outside of the cell
• A hypotonic solution is one in which the
concentration of solutes is greater inside the cell
than outside of it
• A hypertonic solution is one where the
concentration of solutes is greater outside the
cell than inside it
Ion channels
• Ion channels are pore-forming membrane proteins whose
functions include establishing a resting membrane
potential, shaping action potentials and other electrical
signals by gating the flow of ions across the cell
membrane, controlling the flow of ions across secretory
and epithelial cells, and regulating cell volume.
• Ion channels are present in the membranes of all cells.
• Ion channels are considered to be one of the two
traditional classes of ionophoric proteins, with the other
class known as ion transporters (including the sodium-
potassium pump, sodium-calcium exchanger, and
sodium-glucose transport proteins, amongst others).
• Schematic diagram of an ion channel. 1 - channel
domains (typically four per channel), 2 - outer
vestibule, 3 - selectivity filter, 4 - diameter of
selectivity filter, 5 - phosphorylation site, 6 - 
cell membrane.
• There are two distinctive features of ion channels
that differentiate them from other types of ion
transporter proteins:
• The rate of ion transport through the channel is
very high (often 106 ions per second or greater).
• Ions pass through channels down their
electrochemical gradient, which is a function of ion
concentration and membrane potential, "downhill",
without the input (or help) of metabolic energy
(e.g. ATP, co-transport mechanisms, or 
active transport mechanisms).
• Ion channels are integral membrane proteins of membranes that
form the holes in the membrane filled with water.
• The number of ion channels detected in plasma membrane that are
characterized by high specificity, permitting the movement of only
one kind of ions.
• There are the sodium, potassium, calcium and chloride channels.
• Each of them has a so-called selective filter, which is able to allow
pass only certain ions.
The sodium-potassium pump and related diffusion of sodium and
potassium between the extracellular and intracellular space
• The permeability of the ion channel may change due to the presence
of the gate, specific groups of atoms within proteins forming the
channel.
• The conformational change of the gate transferred to the channel from
the open state to the closed and vice versa.
• Mechanisms of regulation of the gate position may be different in
different channels.
• Some of them are opened when the electric potential of the membrane
changed . Other open under the influence of specific chemicals that
perform signaling functions.
 If the process uses chemical energy, such
as from adenosinetriphosphate (ATP), it is
termed primary active transport. 
• Sodium-potassium pump - one of integral
membrane proteins.
• It possesses enzymatic properties and is able to
hydrolyze adenosine triphosphate (ATP), which is
the main source and repository of energy
metabolism in cells. This integral protein called as
sodium-potassium ATPase.
• ATP molecule decomposes into acid molecule of
adenosine diphosphate (ADP) and inorganic
phosphate.
The action of the sodium-potassium pump is an
example of primary active transport.
• Secondary active
transport
involves the use
of an
electrochemical
gradient
An electrochemical gradient
• An electrochemical gradient is a gradient of
electrochemical potential, usually for an ion that
can move across a membrane.

• The gradient consists of two parts, the chemical


gradient, or difference in solute concentration
across a membrane, and the electrical gradient,
or difference in charge across a membrane.
Secondary active transport
• Secondary active transport is a form of active
transport across a biological membrane in
which a transporter protein couples the
movement of an ion (typically Na+ or H+)
down its electrochemical gradient to the uphill
movement of another molecule or ion against a
concentration/electrochemical gradient.
• Thus, energy stored in the electrochemical
gradient of an ion is used to drive the transport
of another solute against a concentration or
electrochemical gradient.
Secondary active transport
• Sodium is the driving ion
for many cotransporters
and exchanger and,
therefore, these transport
proteins may also be
referred to as sodium-
coupled cotransporters.
Figure 1 provide a
summary of secondary
active transport processes.
• For example, the Na+/glucose cotransporter,
found in the small intestine and kidney
proximal tubules, simultaneously transports 2
Na+ ions and 1 glucose molecule into the cell
across the plasma membrane.
Endocytosis is a form of active transport in which a 
cell transports molecules (such as proteins) into the
cell by engulfing them in an energy-using process
EXOCYTOSIS
Thank you for the
attention !!!!!!

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