Three-dimensional structure of a cell

Lecture 3

The main provisions of the cellular theory at the present stage are formulated as follows:

A cell is a structural and functional unit,as well as a unit of development of all living organisms.

Cages have a membrane structure.The nucleus is the main constituent part of the cell.New cells are formed by dividing previously existing cells.Cells of all organisms are similar in their chemical composition,

structure and functions and have a single origin.

The cell membrane system and the cell cytoskeleton provide a unique three-dimensional structure and specialization of cells.

Biological membranes

• These are thin films (membranes) formed by a phospholipid bilayer.

• Any biological membrane is a continuous surface: it has no edges, it closes itself to itself or passes into another membrane.

• The basis of biological membranes is phospholipids.

Four groups of discoveries that have changed the understanding of cellular biological processes:1. Organization of the genome. In eucaryotes, genetic loci are arranged modulo, representing structures from regulatory and coding modules common to the entire genome. This ensures fast assembly of new designs and regulation of gene ensembles.Loci are organized in hierarchical networks, led by the main switch genome, the co-ordinated genes are integrated into different networks: they function in different periods of development and affect a variety of phenotype signs. 2. Reparative possibilities of the cell - a system of reparation at the level of replication, transcription and translation, counteracting accidental physicochemical effects.

Four groups of discoveries that have changed the understanding of cellular biological processes:3. Mobile genetic elements and natural genetic engineering. The work of the immune system is based on the continuous construction of new variants of immunoglobulin molecules based on the action of natural biotechnological systems (enzymes: nuclease, ligase, reverse transcriptase, polymerase, etc.). The same systems use mobile elements to create new inheritable structures. Genetic changes can be massive and orderly (directed). Constant reorganization of the genome is one of the main biological processes.4. Cell information processing. The cell continuously collects and analyzes information about its internal state and external environment, making decisions about growth, movement and differentiation.The process of mitosis is universal in higher organisms and includes three consecutive stages: preparation for division, replication of chromosomes and completion of cell division. The analysis of the gene control of these phases led to the discovery of special points in which the cell checks whether there has been a repair of the disturbances in the DNA structure at the previous stage or not. If errors are not corrected, the next step will not begin. When damage can not be eliminated, a genetically programmed system of cell death, or apoptosis, is triggered.

6

Cell membrane

Functions Cells organells

Barrier, supporting, protective

Diffusion and

OsmosisLight

diffusionActive

transport

EndocytoseEcsocytose

Derivation of metabolites and absorption of nutrientsHormonal and neurotransmitter reception

Selective permeability

Phospholipid bilayer

Proteins and glycoproteins

Small molecules

Functionscellularmembranes

Transport(excretion / absorption)

Structure

Separation of the body from

the environmentBig molecules

1

2

3

0

Hydrophilehead

cholesterol-boosted area

relatively mobile area

гидрофобный хвост

Choline

Cells membrane chemical composition , %

Lipids 25-60

Proteins 40-75

Carbohydrates 2-10

In the cell membrane there are three kinds of lipids:

phospholipidsglycolipidscholesterol.

All three types of lipids are amphiphatic, i.e. have a hydrophilic head andhydrophobic tails. The length of the tail can range from 14 to 24 carbon atoms.Ampiphatic molecules in the aquatic environment are aggregated in two ways:in the form of spherical micelles, with tails inwardin the form of bilayer films, with tails located between the layers of hydrophilicheads.When the lipid bilayer is closed, a closed compartments compartment is formed,thereby avoiding contact of hydrophobic ends with water.

6-12нм

Rotation

Lateral diffusion

Vertical vibration

Protrusion

Compression

Stretching

Bending fluctuations

Transverse fluctuations

Movement of lipids in the bilayer

Prohibition of transitions from layer to layerThe chemical composition of the layers is asymmetric!

When heated to body temperature, the membrane thickness fluctuates within 8% every 100 ns, which is 30 times slower in comparison with non-biological samples.

(picture Nagao / NIST)

Woodka A.C., Butler P.D., Porcar L., Farago B., Nagao M. Lipid bilayers and membrane dynamics: Insight into thickness fluctuations// Physical Review Letters. – 2012. – Vol. 9, N 5. DOI: 10.1103/PhysRevLett.109.058102,

Properties of bilayerindividual molecules can move freely within their

monolayer, but can not practically move to the second monolayer (for a single molecule, such a transition is possible not more than once in two weeks);bilayer is asymmetric. This property is ensured on the

one hand by the impossibility of vertical diffusion of lipid molecules, on the other hand, by a significant chemical difference in the lipid composition of each monolayer:in human erythrocytes, most of the lipid molecules

ending in choline are located in the outer half of the bilayer;glycolipids, oligosaccharide-containing lipids, are

always located in the outer half of the bilayer, so that the sugar portion faces outwards;The negatively charged phosphatidylserine is always

located in the inner half of the bilayer.

Plasmatic membrane

Cell membrane system

Functions of the plasma membranedelimits each cell from the environment;determines the size of the cell and ensures the preservation

of significant differences between the cell content and the environment, ensuring the consistency of cellular composition and structure;serves as a highly selective filter that maintains the

concentration gradient of ions and ensures the directional flow of nutrients to the interior of the cell and the products of vital activity from the cell;provides information interaction of the cell with the external

environment;unites individual cells in tissues;internal membranes of cells, provide the possibility of

simultaneous implementation of incompatible processes, for example, synthesis and destruction of the same substance occur in different parts of the cell (compartments), the synthesis of acids and bases in the cell is also spatially separated.

Mechanisms of information transfer by plasmalemma

Mechanical transmission:Waves of mechanophysical deformationInteraction of glycocalyles of neighboring cellsElectrical (desmosomes and efaps)Electrochemical (synapses) - hydrophilic signaling

moleculesSimple transmembrane diffusion of hydrophobic

signaling moleculesExchange (slotted contacts)

Electrical potential of the membrane

where: R is the universal gas constant,T is the thermodynamic temperature,z is the electric charge of the ion,F is the Faraday constant,[K +] i and [K +] o - intra- and extracellular concentrations of

potassium ions, respectively.But if we take into account the membrane permeability for ions: PK, PNa, PCl - permeability for potassium, sodium and chlorine ions respectively, we get the following equation

𝜑𝜑𝑚𝑚 = −𝑅𝑅 ⋅ 𝑇𝑇𝑧𝑧 ⋅ 𝐹𝐹

⋅ ln𝐾𝐾+

𝑖𝑖

𝐾𝐾+0

𝜑𝜑𝑚𝑚 = −𝑅𝑅 ⋅ 𝑇𝑇𝑧𝑧 ⋅ 𝐹𝐹

⋅ ln𝑃𝑃𝑁𝑁𝑁𝑁+ ⋅ 𝑁𝑁𝑁𝑁+ 𝑖𝑖 +𝑃𝑃𝐾𝐾+ ⋅ 𝐾𝐾+

𝑖𝑖 + 𝑃𝑃𝐶𝐶𝐶𝐶− ⋅ 𝐶𝐶𝐶𝐶− 𝑖𝑖

𝑃𝑃𝑁𝑁𝑁𝑁+ ⋅ 𝑁𝑁𝑁𝑁+ 𝑜𝑜 +𝑃𝑃𝐾𝐾+ ⋅ 𝐾𝐾+𝑜𝑜 + 𝑃𝑃𝐶𝐶𝐶𝐶− ⋅ 𝐶𝐶𝐶𝐶− 𝑜𝑜

Goldmann-Hodgkin equation Рк : РNa : PCl = 1 : 0,04 : 0,45.[K+]вн · [CI-]вн = [K+]нар · [CI-]нар

Nucleus membrane

Endoplasmaticreticulum

Lysosome and peroxisome

Cell membrane system

V. A. Kozlov, full Bilogical Science doctor, Ph.D. Medical Science, professor 21

Nucleus

V. A. Kozlov, full Bilogical Science doctor, Ph.D. Medical Science, professor 22

The membrane of the nucleus is double-layered

Functions of the cell nucleus• Storage of hereditary material, genes in the form of

long and thin DNA strands are called chromatin.• Storage of proteins and miRNA in the nucleolus.• The nucleus is the site for the transcription of mRNA.• The mRNA splice compart- ment.• Exchange of hereditary information between the

nucleus and the rest of the cell.• Reduplication of hereditary material.• Information exchange (mobile elements of the

genome).• Selective transport of regulatory factors and energy

molecules through nuclear pores.• Production of ribosomal rRNA.

24

Nucleus

1 - 4 outside the core

The production of ribosomal RNA (rRNA)

25

Endoplasmatic reticulum (EPR)

26

3D reconstruction of the endoplasmic cell network site

Nucleus membrane

Chromatine

The site of mitochondria

Endoplasmaticreticulum

EPR functionransport of proteins and other carbohydrates to other organelles: lysosomes, Golgi apparatus, peroxisomes, mitochondria, plasma membrane.Participates in the formation of the cytoskeleton.Provides an increase in surface area for cellular reactions.Helps in the formation of the nuclear envelope in cell division.Synthesis of proteins, lipids, glycogen and steroids: cholesterol, progesterone, testosterone, estrogens, etc.

Molecular crouding (cell level)Crowding is a crush in the crowd, gathering in a crowd full of jam.The effect of excluded volume is observed in a medium containing high concentrations of macromolecules (50-400 mg / ml) [1-3], but the concentration of macromolecules of one species is relatively small.Together, the macromolecules present in the cell occupy a significant part of the volume of the medium (up to 40%), which causes a decrease in the volume of the compartment and the number of degrees of freedom for the displacement and orientation of macro- and small molecules in space.The crowding effect is accompanied by mutual impenetrability of all molecules of dissolved substances. This nonspecific steric repulsion is always present, regardless of other interactions, such as attraction or repulsion between molecules in solution.Crowding is like gravity. There are no beings in the cells of which it would not be observed.

1. Fulton, A.B. (1982) Cell, 30, 345–347. 2. Zimmerman, S.B., and Trach, S.O. (1991) J. Mol. Biol., 222, 599–620. 3. Ellis, R.J., and Minton, A.P. (2003) Nature, 425, 27–28.

H2N

HN

HN

O

O

O

NH

NH

HN

NH

O

O

O

HN HN

OH

O

O O

OH

OH

SH

H2N

OH

H2N

O

O

Golgi apparatus

V. A. Kozlov, full Bilogical Science doctor, Ph.D. Medical Science, professor 30

The Golgi apparatus functionsThe cells synthesize a huge number of different macromolecules, the Golgi apparatus participates in:changing, sorting and packaging of macromolecules synthesized by cells for use in secretion or for use within the cell.post-translational modification of proteinstransport of lipids in the cell.formation of lysosomes.import of substances and nucleotides from the cytosol of cells.determination of the final destination of proteins.This place:production of proteoglycans and carbohydrates.sulfatation of some molecules.phosphorylation of some molecules.

Lysosome

32

Only found in animal cells

FunctionsAccumulation of enzymes for intracellular digestionRecycling of cellular wasteParticipation in the reactions of apoptosis and necrosis

Violation of the function of lysosomes is the cause of 50 diseases

Peroxysome

33

They are found in both animals and plant cellsContain more than 50 enzymesH2O2 is produced (danger!)Absorption and degradation of fatty acids and nucleic acidsConvert free radicals to H2O2Convert H2O2 to harmless H2O and O2 using catalaseContain digestive enzymes

Cytoskeleton

34

35

Cytoskeleton

Functions

Defines, attaches and maintains the shape of the cell.Provides mechanical resistance to deformation.Interacts with the matrix and provides overall stability.The guide element used by the cell for directional transport of molecules along the ∆ϕ-gradient.The transport pathway of intracellular signaling molecules.Separation of chromosomes during cell division, and later separation of daughter cells during cytokinesis.Provides the basis for the organization of cellular components.Forms specialized structures: flagella, cilia, podosomes, etc.Allows cells to support the environment.Provides the synthesis of structural elements of the cell wall.

Ribosome

36

Function

Protein synthesis

Mitochondria

37Two bilayer membranes

3D reconstruction of mitochondria

Márquez Neila P., Baumela L. González-Soriano J., Rodríguez J.R., DeFelipe J., Merchán-Pérez Á. A Fast Method for the Segmentation of Synaptic Junctions and Mitochondria in Serial Electron Microscopic Images of the Brain // Neuroinformatics. 2016. V. 14(2). 235-250. doi: 10.1007/s12021-015-9288-z.

Egner, A., S. Jakobs and S. W. Hell (2002). "Fast 100-nm resolution 3D-microscope reveals structural plasticity of mitochondria in live yeast." Proc. Natl. Acad. Sci. USA 99: 3370-3375.

Structure of mitochondriaOuter membrane:smooth and consists of equal amounts of phospholipids and proteins.has a large number of special proteins, known as porins.porins are integral membrane proteins, provide a transmembrane transfer of molecules up to 5000 daltons in weight.is freely permeable to nutrients, molecules, ions, the energy of molecules, like the molecules ATP and ADP.

Structure of mitochondriaInner diaphragm:more complex in structure - folds many times in folds, called cristae, which increases the inner surface.is the site of the dislocation of proteins involved in the production of ATP molecules (electron transfer chains).the inner surface of the membrane is the site of the dislocation of the proteins of the Krebs cycle (oxygen glycolysis).provides the conjugation of the production of ATP and oxidation of pyruvic acid, as well as the conjugation of oxidation and reduction of malic and aspartic acids.unlike the outer membrane, it is strictly one-sided permeable, it transmits only oxygen, ATP and water.

Structure of mitochondriaThe intermembrane spaceThis space between the outer and inner membranes of the mitochondria, it has the same composition as in the cytoplasm of the cell. There is a difference in protein content in the intermembrane space.Matrix is the inner space of the inner membrane, contains a complex mixture of proteins and enzymes, mitochondrial ribosomes, tRNA and mitochondrial ring DNA.Codon Mitochondria Universal codeUGA Tryptophan Stop codonAUA Methionine IsoleucineAGAAGG

Stop codon Arginin

Functions of mitochondriaEnergy production is oxidative phosphorylation.Maintaining normal concentrationcalcium ions inside compartments.Synthesis of steroids (cholesterol)and steroid hormones (progesterone, testosterone and

estrogens).Synthesis of pentose.Detoxification of ammonia.Apoptosis or programmed cell death.Mitochondrial dysfunction due to anomalies of their

genome is the cause of many hereditary diseases.The mitochondrial genome is susceptible to significant

modifications during ontogenesis.

Achilleas Frangakis, European Molecular Biology Laboratory, Heidelberg, Germany. Reproduced with permission from Nature Publishing Group; Al-Amoudi et al, (2007) Nature 450: 832–837.

area of intercellular contacts (sandy-brown),core and nuclear envelope (blue)pores (red),microtubules (green),mitochondria (violet)endoplasmic reticulum (steel blue)

© https://creativecommons.org/licenses/by-nc-nd/2.0/

3D reconstruction of brain neurons

3D reconstruction of murine neuron organelles, layered scanning electron microscopy (ATUM-SEM). White: core, yellow: mitochondria, blue: Golgi apparatus, black: lysosomes. The endoplasmic reticulum is not shown.

http://lichtmanlab.fas.harvard.edu/Image credit: Daniel Berger, Lichtman lab

What will happen to the water if the bottle is reduced only tenfold?The diameter of the neck decreased by a factor of 10, the surface tension is also the same, and the mass of the wine is about 103 times. Such a mass can no longer overcome the surface tension at the liquid-air interface.

On average, the cell contains about 7.7 × 109 molecules of water. The surface tension of this volume of water is 2.8 × 104 n / m. For this reason, 7.7 × 109 water molecules do not exhibit the fluidity properties and will resemble gel in their physical properties, which implies that, given the cell size, the gravity in the cells does not play a significant role. That is, the contents of the cell are in "weightlessness" conditions, due to electrostatic forces, the electromagnetic field created by self-induction of ions moving relative to each other, dipoles and charged molecules, surface tension and viscous friction.

Nanoscale cellular effects1. All cellular structures have nanoscale, so in the cell

should be observed nanoeffects.2. All our ideas about the chemistry of aqueous

solutions are absolutely inapplicable to the cell, because of its size, and require revision.

3. At a distance of about 120-150 nm from the solid surfaces - membranes - water is ordered, it also forms 2-3 ordered layers near the biomolecules. For this reason, the water in the cell, apparently, does not flow.

4. Molecules in the cell must be counted on pieces, such a concept as the concentration of any molecules to the cell is not applicable.

Due to the presence of croding effect and strong surface tension, the reactions in the cell pass almost as in a solid.

Classical aqueous biochemistry is very far from the real cellular processes.

How do cell sizes correlate with biomolecules?There are 1013 pieces of molecules in the cell, however:In the cell, on average, less than 4 molecules of growth hormone or chemoattractant. Even in a vast area around the cell, for example 10-3 cm (26 times the cell volume), at the usual concentration of the hormone (1 pM), there will be only about 8 molecules.The number of receptors is also measured by pieces. For example, the number of insulin receptors on different cells varies from 40 (erythrocytes) to 300,000 (hepatocytes and lipocytes) pieces - not very much.In the volume of E. coli, for example, only 120 free protons. Then, what is the intracellular pH of the medium?