Extracellular Matrix and Cancer

All cells, bacteria and viruses have a wrapping membrane formed by lipid bilayers. I don't know exactly how it grows back after a cellular division, but i believe it is the fundamental "brick" of life. Everything that lives in the animal kingdom have to have one. It is very fragile, like a soap bubble. Can read for further details.

The thickness of this universal bio material is known, it is two molecules thick or about 4 nm (nano meter or 1/1000 microns or 10 to the power -9 meters). For comparison, the size of a diamond cubic crystal made of 8 atoms is about 0.35 nm.

One of the methods of visualizing a virus within a tissue is by freezing and cutting that piece containing viruses with a micro-tome equipped with a knife made of diamond. However you cannot sharpen diamond to obtain an edge one atom thick, and even if you could it would break before cutting anything. One of the smallest commercially available diamond knife is about 12 atoms or 2 nm radius or 4 nm thick.

Because of that a cross section through a cell's or virus's membrane would be more of a tear than a cut.

Most viruses have around 100 nm diameter. To see a cross section of a virus you have to cut slices of the tissue suspected to have viruses in it and then you look under electron microscope to see if you caught/cut a virus in two.

Eukariotic cells are those which made up multicellular organisms. Their two molecule thick lipid bylayer membrane is very fragile but they are encapsulated in collagen extracellular tissue (or cellulose in case of plants) that also holds an organ together and has some mechanical resistance.

Here are images of collagen extracellular matrices in cut cross sections in various stages of degradation because of induced illnesses in mice, last one being most porous, after they have been stripped of cells with some chemicals.

Usually represented through graphs, there are also images of cross sections of whole cells taken under electron microscope, though is hard to catch in a single image all types of organelles within one single cell in a cut sample. But i would assume if you have enough time and patience you would find a cell that has been cut in such a way it has all of those visible.

Coincidentally this cell is seen with two open vesicles in the lower right side which means the cell is dying because some of its organelles are already used to produce viruses. It can also be a cultured cell, that is not wrapped yet in a connective tissue matrix.

To me it is hard to believe a cell would produce something that would infect and kill other cell, that is viruses.

But how most viruses that are enveloped only in a fragile bylayer membrane can escape the hard collagen connective tissue enclosure of the cell. I believe the answer probably is viruses can only propagate within already damaged tissue or weakened or porous matrix which is not intact and can be an evolutionary mechanism through which cells that are not completely encapsulated are killed. (2 micrometers mean 2000 nanometers).

There is a type of cells that specialize in maintaining and regenerating the connective tissue. They are called fibroblasts. However sometimes tissues cannot be repaired and they are replaced with scar tissues which is mostly made of collagen like in the case of cirrhosis of the liver. But there are no fiberblasts in the extracellular matrix surrounding cells. That one is secreted by the cells themselves.

But it could happen some people are so depleted of collagen from previous repairs like in case in chronic ulcerations, or simply a poor diet, that their cellular matrix is so thin is permeable to things as fragile as viruses. One way to know is examining old scars that used to be firm and then turned into very soft tissue.

Once the matrix become permeable, not only viruses and bacteria but the cells themselves start to penetrate and divide outside, right the border of the matrix, especially in weakened or damaged areas and if they are too many close to each other they start building a different kind of matrix we all know as cancer. Unlike viruses and bacteria they are not recognized as harmful but your organism's immune system.

However it is unclear to me from all i could find how cells divide inside the extracellular matrix where every cell seems to have its own place made of collagen fiber. 

It is obvious there is not enough room for two daughter cells inside a single "room", one of them has to die. I would assume that after division there is a competition between the two daughters and only the most viable survives. But if cells start dividing outside the matrix, they will all probably live for ever inculcating the mutant ones and the ones closest to the old matrix will start building their own aberrant matrix.

Could it be peaks during chemo kill the cells that are dividing freely just outside the matrix more than the ones inside.

...

It is known that collagen fibers are too big to penetrate human intestine. All it can go in your blood stream within a healthy intestine is broken down through digestion small molecules of monosaccharides, amino-acids, fatty acids and minerals.

However, if you take collagen supplements or eat collagen rich foods like bone broth or hot dogs, those are broken down in your intestine during digestion to the exact type of amino-acids and minerals needed by the fibroblasts or cells to produce collagen.

I believe a healthy cellular matrix in all organs is key in cancer prevention and it can be maintained through a proper diet and also by treating all chronic inflammations and ulcerations in your body that are usually caused by an unavoidable toxic environment with dust, mold and bacteria.

May 29

10:28 Just got home and had to move the truck because Saturday i found another warning ticket saying that it will be towed Tuesday.

In this complex we only have one designated parking spot. There are a number of visitors spots, about 15% of the total that people are competing over, to park their second car. However from time to time, if the car is parked for too long on a visitor spot, they will put a warning sticker on your car. My truck was on the same visitor spot since last Thursday, when i last used it, or for two days, however it was in that spot before Thursday as i could not find. Some people don't move their vehicles from visitors spots for weeks. Some just exchange spots with others also on visitor spots.

I write this because tonight the spot next to ours, belonging upstairs was empty (it was used by other people in the last few days) because nobody lives upstairs nowadays and i parked my truck there, for a few hours, or until 4:30 Tuesday morning. I used that spot in the past when that apartment upstairs was vacated and once i was told not to use it anymore.

The alternative is to move it at the Meridian parking lot at the street until morning when i can park it here after Angela leaves, but there i had a number of problems, including a stolen wheel and catalytic. So i have no emotions free alternative tonight.

Earlier. Yesterday and today i avoided a number of ready made accidents (highest on a 24 hours period so far). They all would have been my fault of course. But maybe the most interesting was in Florence Oregon. I came out of a street onto a boulevard. There was this gray older van possibly a VW but second generation (bigger, more solid, square at corners, maybe 80s) coming from the left, at least 300 ft away.

Until i accelerated to speed limit +10 it caught up with me, must have been speeding big time, as i saw it on the mirror only ft away, though the mirror was on night mode since earlier (a long story, somebody with an RV was annoying me when in a parking lot and turned not to see him anymore). In that moment i accelerated more and narrowly escaped. Would have been my fault (going too slow, getting in front of her).

At the intersection i was waiting for green (didn't make a right turn on red or couldn't because of traffic) and it caught up with me on the other lane and looked and guess who it was. It was the artist known as Lady Gaga though i didn't recognized her at first and gave her the finger in frustration and she tried to keep her cool and smile large at me as only she could, making a gesture with her hands claiming ignorance. "What?". I was telling Angela. No cop in his right mind would arrest Lady Gaga for trying to create an accident.

The combined crimes that describe what she did including conspiracy with others to commit those would total probably life in prison. However there is a possibility she was behind the wheel of a retrofitted self driving vehicle (the gesture with her hands above the wheel).

I now remember that yesterday when i left i got behind an SUV with a vine Oregon LP saying GAGAS.Also the car was messed with since i last drove it. All electrical connections to battery and alternator were weakened and contaminated. Had to tighten the battery connectors one by one, and stopped several times, and also cleaned the alternator connector with alcohol (did it only this morning) to make it work back at 44 mpg on a highway (without having to stop, a stop and/or idling would affect that).

Two weeks ago i took a picture of the left front brakes, and though i had at least two more mm or 20k miles to go until that angled part ends but today the plates look much more thinner, like i have to replace them right away. Amazing how far the original ceramic plate went (102kmiles). However last 30k were done by me mostly on highways (outside city) when brakes are not used as much per mile. No sound from the indicator. I'll see tomorrow.

Also, for months now, any vehicle that gets behind me comes too close. When i try to stop and let them pass and restart (that cost me on mpg), others come right away and do the same as they were organized (criminals).

We made a reservation a while ago at a hotel for the week June 11-27, Angela made a vacation request at the same time, however no response yet.

This morning Angela started the phone in the bathroom at the hotel in the same that i was with the meter in my hand next to the door trying to keep away from the oven while heating water for tea and noodles (that was much more leaky than others before). But i noticed the meter was not beeping or showing anything during startup of her phone, or one meter away.

I attributed that to the fact the tower was less than a quarter of mile away and phone was on lowest emitting setting.

I decided to use it myself (her phone not mine) to modify something on the blog on the post with... cell phones radiation (remembered about the polar lipid bylayer i once wrote in a post about). However when i started it (Angela stopped it as per our new rules) the beeper went crazy (never saw readings so high from a phone before, even from 3-4 meters away), probably got connected to another more distant tower and i had to refuge in the other corner of the room still getting high readings until startup and initial protocol with tower ended and then when i tried to approach it the emission power was still too high and i just shut it down.

The hotel room was reasonably clean except for the windows. There was a thick layer of pickled smoke algae on the outside. I think it happens only in building D. I tried to clean it but could only picked some of it. There was smoke coming from fires on the beach. A number of people on the beach but only in front of our room, and they all seemed Japanese. After eating and having a few drinks i fell asleep and woke up in an hour or so very sick, probably because of nose congestion. I almost could not walk to the casino to find Angela.

Gradually got better inside the casino where there was no smoke and after breathing on my mouth for an hour or so. Went to sleep at 2:30. In the morning the exaggerated, unexplained, most likely intentional noises from 5 surrounding rooms woke me a number of times. Could not sleep between 5:30 and 7:30 because my right eye was itching badly from cleaning the windows and because i was thinking of the polar lipid bylayer of my poor cells that have been exposed for so long. Slept maybe 6 hours in about 10 fragments. After that i drove for about 220 miles.

Won a little, for the first time maybe since Easter which confirms my theory. They set the machines loose on holidays.

12:25 Gaga, Giga (Hertz). It totally makes sense.

Cell Phones For Your Cells

There are at least two mechanisms the food gets heated by in a microwave oven.

One is vibrating of the polarized water molecules (Official main theory). The electromagnetic radiation (radio waves) from an antenna powered by a device called magnetron located inside the oven, which radiation is basically an electromagnetic field that changes polarity billions of times a second (2.4 billions in this case, to be more precise), makes the water molecules inside the oven spin.

Little is known about how the spinning energy of a polar molecule turns to linear motion energy which is heat. I would assume through knocking out of adjacent molecules by the lobes of rotating ones.

The membrane of a living cell is made by a layer of polar molecules called lipid bilayer. It is two molecules thick and the molecules arrange with the polar end on the opposite sides. There are known effects of a static electric and high frequency electric field (microwaves) on a lipid bilayer.

Though these molecules are polar at one end only, they will also oscillate in the presence of the oscillating electric component of a microwave radiation.

The other is through the more known mechanism of inducing electric currents. Electrons are knocked out of their orbits and start moving around alongside the electric component of the field but also due to the magnetic component (Eddy currents), again, back and forth, with the same frequency. Same goes for the remaining ions orphaned of electrons. Heat is caused by the resistance to the flow to the motion of electrons and by the motion of the ions in the opposite direction.

Salt and other electrolytes make water more conductive. Due to this fact biological tissues that have more salt, like blood and blood vessels are heated more.

I would think the second mechanism transfers to food more energy from the antenna inside the oven then the first.

Microwave ovens leak radiation in the order of magnitude of cell phones total emitting power therefore a measurable leaked signal from a microwave oven can reach distances in the order of miles. For this reason there was a need to establish a band of frequencies chosen by the manufacturers that was agreed not to be licensed for communications, just above 2.4 Ghz.

It is also likely that this frequency was chosen by the manufacturers for reason of being most penetrating in biological tissues, for uniform heating.

In is also said that cell phone manufacturers have also chosen this unlicensed band initially not allocated for communications to cut through the bureaucracy of getting a license for each channel though i doubt they would have had problems with FCC or other regulating authorities. They don't use the band continuously, but divided it into a number of fixed frequencies called channels, that are in the range of hundreds.

I have made too many times the mistake of assuming that people know what i already knew at the beginning of doing a research or explaining something new. That is since the time i took a course of Inventics in college. When doing the paperwork for an invention, you have to concentrate to demonstrate the new things you bring in based on the most advanced already existing knowledge in that field and not start from basics. Also because an invention is usually addressed to specialists hired by the patenting authority, the so called examiners.

A cell phone is a two way radio device, the same as a walkie talkie. There are differences though. The communication is not done between two phones directly but with the help of one or two towers. Once a call is being made, the network dispatches the call to another tower nearest to the destination or to a landline.

The channels or frequencies (there are always two, emitting and receiving, of full duplex) are being chosen by negotiations with the tower, after "listening" at both ends and finding a free or noise free channel. The channels and even the towers can be switched automatically during the conversation (if by example a channel becomes noisy or the phone is moving like being in a car) without the user noticing. It is said though i doubt it this technology called frequency hopping was co-invented by Austrian born Hollywood actress Hedy Lamarr, once called "the most beautiful woman on screen".

The signal emitted by the cell phone which again is in the range of 2.4 GHz, overlapping the unlicensed band used by microwave ovens has to beat the distance to the tower. However about half of the signal is absorbed by your body, head first.

The phone has a number of automatic emitting power settings, between 0.3 and 3 Watts that are used according to the distance to the tower shown by the number of bars of signal. The difference between first and last is big, and 3 watts is about 3 times the amount of leaked power from a microwave oven (those vary according to the amount of food heated and the position on plate).

3 to 4 minutes is enough to heat most foods the size of a small brain from frozen to boiling in a medium size microwave of 1000 watts full power.

The exposure from a cell phone can be 300 times less than the power needed for heating frozen food inside the oven but the time of exposure to a cell phone radiation during a day can be up to 20 times more for one hour and now people are checking social media or listening to music, that can be hours a day giving a total daily exposure comparable to that of heating frozen food in the oven in 3-4 minutes.

And yes, that exposure is too low to boil your cells (only one case heard of), only enough to re or disorganize the lipid bylayer, disrupt enzymatic processes, damage DNA, etc.

But the heating is not even. There are organs like pancreas that are full of electrolytes (sodium carbonate), stomach (hydrochloric acid), blood vessels (salt) etc.. And it's not only heating. Some lengthy nerves axons are also conductive.

Think about. While you still can.

Now i understand people can't do without them anymore. However there are easy doable ways to avoid most of it. One is using the bluetooth headsets that theoretically uses about 1000 times less power than a cell phone though if you asked me i would say that like in the case of exposure to lead, there are no safe levels.

At home and/or work you can put the phone at least 2 meters away and use it on bluetooth. You can use other devices for checking social media, like a laptop or a tablet which of course need to be connected to the router through a cable rather than wi-fi which has an emitting power comparable to cell phones (and yes in the same unlicensed penetrating band).

Ultimately can consider getting back to a landline and use it with a chorded receiver.

Also it is easy to get rid of most wi-fi emitters in your home, that are of comparable emitting powers with the phones, like the TVs by using the built in ethernet plugs and buying a 10 dollars cable. You will also get better speed by switching to those.

The differences in emitting power of different brands of phones and operating systems (Android, Apple) are minor, they all have to beat the distance to the towers.

The biological long term effects of low level microwave radiation, like from any radiation, are cumulative throughout one's lifetime, which means once enough number of capillaries, small blood vessels and cells are destroyed your body can not recover from that anymore, due to lack of oxygen and/or nutrients at that tissue level.

Frequent, painful, hard to heal infections that lead to so called chronic illnesses including pancreatitis, need to replace articulations, like hip replacement, neurological problems like balance (dizziness), heart problems like arrhythmia, depression and dementia.

Size Matters

Do you think the cells of an elephant would be larger than the cells of a rat? Do you think the cisternae of an Endothelial Type II cell are bigger than those of a white blood cell?

One would think internet should be full with Electron Microscope (EM) images of COVID inside a human cell. Just several, inconclusive. I fail to see in this image the bronchitis coronavirus virions forming inside of a cisterna. Even the (sub)title of the image says: "assembling in a Golgi region"

Spent most of the morning searching for things like what type of human cells are attacked first by COVID and how COVID multiplies after taking over those cells. However i could not find EM images with those cells. All i could find was this. Here, an Endothelial Type II cell is shown sitting at the bottom (top in image) of an alveolar sack and its internal structure which includes a Golgi apparatus.

It is within this type of cell the exchange of gases between air and blood occur. Oxygen passes from air to blood and CO2 back in the air.

Current theories say COVID is packed (assembled) inside of organelles of human cells known as Golgi apparatus, more precisely in a structure of this organelle called cisterna. Prior entering the cisternae, in the intermediate endothelian reticulum or ER, ribosomes, enzyme like structures made of two proteins which normally produce proteins, one of the main functions of most cells, provides proteins for the viruses. Normally specific parts of RNA (which is the same for every cell of our body) from cell's nucleus is used by ribosomes as a blue print for cell specific proteins, then proteins made by ribosomes are evacuated when vesicles form at the end of Golgi apparatus cisternae and those vesicles are transported at the surface of the cell and evacuated in the intracellular space to do whatever.

Same theories say that in case of infection with COVID these normal functions of the ER and Golgi apparatus are hijacked to produce not only the spike protein for the virus but the whole thing, that is envelope, membrane, M and S proteins. Viruses packed inside the complex are wrapped in vesicles then evacuated delivered to the surface of the cell through the same mechanism.

While i understand that viral RNA can be used instead of nucleus RNA in ribosomes to produce proteins (though i believe each type of cell has its own unique type of ribosome, which can have a limited "range" or what type of proteins can produce), i fail to understand how the Golgi apparatus and ER functions are changed (by the virus) to also produce membranes and envelopes.

I could not find an electron microscope image of the Golgi apparatus with cisternae for an Endotelial Type II cell, all i could find was one for white cells. The scale bar show that the thickness of cisternae and vesicles are smaller than 100 nm, the average size of a coronavirus, and that without the spike protein.


Ok it wouldn't be fair if i didn't put here what i found later. Vero is a type of "standard" lab grown cell coming from a single lineage descending from the liver cells of a specific monkey. Shown is a herpes virion building up at the end of a much smaller cisterna inside a vero cell. Looking at the image makes me think the cisterna receives the virion RNA from nucleus and provides the membrane, envelope, the M, S and spike protein, like it actually had this functionality and viruses could actually play an evolutionary role. But then in the explanation i see the word "budding" (c). Then i see several virions inside a single vacuole ready to be lifted at the surface of the cell.

From now on it becomes confusing, cause if you asked google, it says viruses are assembled inside golgi, if you follow this article, it's a different story. In both cases it seems obvious to me that the virus does not contain enough information to "hijack" or "reprogram" the cell into doing all this, but the cells are already adapted to do this since billion years ago to do it, like it had this functionality and viruses could play key roles in evolutionary process. Lipid membrane, envelope is provided by the ER and golgi, which pre-exists in host's cells.

One thing to mention here. When i was thinking that the cell itself could actually have this functionality and especially when i used the word "evolutionary", the man upstairs started to yell as much as one could yell obscenities in Spanish or Portuguese. Can not say i actually got scared and stopped reading and following ideas especially because apartment is filled with smoke from the walls. Got to finish or even re-write this post later. I would imagine the catholic point of view on this. God could not have created a human being (in its own resemblance) that produces viruses to infect others. Then i remembered the logo of the management firm of the apartment complex, and its resemblance to Dominican Province of the Philippines logo.

And one more thing. Here is a crop from last EM image.

Again because of the search results i made while writing this blog post (don't have time to write a pre-version first, than read it and re-write it if necessary), the whole idea behind this post which i started thinking the cisternae of the golgi aparatus are too small for the COVID virus, has changed and it would be necesary to re-write it. But then again it took me half day to search and write. It seems there are contradicting theories about how a virus is formed inside a cell. It seems the existing theories contradict selves. It seems there is very little "fundamental" research behind how viruses are formed, etc.. All together is too much for me and the scope of a blog post.

Plasma Membrane in Prokariotes, Eukariotes, Viruses

"At some point in early evolution [4 billion years ago], life became cellular. Assuming that this step was required for the origin of life, there would necessarily be a pre-existing source of amphihilic compounds capable of assembling into membranous compartments."

"Anyone who has blown a soap bubble has made a self-assembled membrane. Soaps are monocarboxylic acids, and a soap bubble is a metastable structure with a monolayer of ionic fatty acids on the outside and inside surface. The hydrocarbon chains are directed outward, and the hydrophilic head groups stabilize a thin layer of micelles and water on the interior of the membrane. Soap molecules also assemble into microscopic vesicles in aqueous phases, but the membranes are bilayers with the hydrocarbon chains directed inward. Self-assembly of amphiphilic molecules like soap is so common that it is not difficult to imagine that similar molecules, if available, would form membranous compartments on the prebiotic Earth."

"A lipid bilayer is a biological membrane consisting of two layers of lipid molecules. Each lipid molecule, or phospholipid, contains a hydrophilic head and a hydrophobic tail. The tail regions, being repelled by water and slightly attracted to each other, congregate together."

"The bilayer structure is attributable to the special properties of the lipid molecules, which cause them to assemble spontaneously into bilayers even under simple artificial conditions."

"Cells fall into one of two broad categories: prokaryotic and eukaryotic. The predominantly single-celled organisms of the domains Bacteria and Archaea are classified as prokaryotes (pro– = before; –karyon– = nucleus). Animal cells, plant cells, fungi, and protists are eukaryotes (eu– = true)."

"The oldest evidence of eukaryotes is from 2.7 billion years ago. Scientists believe that a nucleus and other organelles inside a eukaryotic cell formed when one prokaryotic organism engulfed another, which then lived inside and contributed to the functioning of its host."

They both do have a membrane made of a lipid bylayer. The "housing" of every living cell. However prokaryotes have an extra cell wall.

"Cell Walls: Most prokaryotic cells have a rigid cell wall that surrounds the plasma [lipid bylayer] membrane and gives shape to the organism. In eukaryotes, vertebrates don't have a cell wall but plants do." Jul 11, 2019

Here is a diagram of an eukariote focused on the membrane. You can see the two layers of phospholipids (with red "heads") that stay together by means hydration repulsion , hydrophobic attraction and van der Waals forces. It is this combination of forces and existence of polar phospholipids that makes possible all life.

However, as stated above, eukariotes in vertebrates lack a cell wall. To protect the fragile lipid bylayer they have to secrete a protective layer of proteins, mainly collagen, that forms what we call the extracellular matrix.

Antibiotics rely on the fact that bacteria are prokaryotes and have a cell wall (with some exceptions, but those are parasitic or live only inside host cells) and animal cells are eukaryotes. They prevent building of new bacterial cell wall made of peptidoglycan after bacterial (cellular) division. New bacteria cannot survive without a cell wall as they can't secrete an extracellular matrix.

Viruses are not cells. They are a molecular structure made of a lipid bylayer with binding proteins on the outside, ARN fragments and proteins (sometimes in a capsid) on the inside and they lack both cell walls as in prokaryotic cells and extracellular matrix as in eukaryotic cells.

Question. How coronaviruses "survive" in the environment, outside and inside of a host, without a cell wall or an extracellular matrix?

One possible answer is when they leave the host they can only "survive" inside fragments of extracellular matrix from damaged areas of the body or engulfed in mucus secretions.

More on Lipid Bylayer

Following

Feel patient enough today to be able to read a scientific article?

"This thin, flexible, and potentially very fragile structure is all that stands between the interior of the cell and the environment." (Yeah, cells could not form organs if it wasn't for the extra-cellular matrix made of collagen, a very strong protein).

"Most books mention that membranes have a typical "lipid bilayer," but why lipids, why should it be a bilayer, and how was this basic structure determined? Although it is now generally taken for granted that membranes are based on the presence of a lipid bilayer, that was not always the case. Early experiments, often by physicists, led to the understanding that the cell membrane was lipid in nature. A key experiment using the Langmuir trough provided the basis for accepting that the membrane is a bilayer and laid the groundwork for the current model of membrane structure."

"Working in her kitchen, and with no formal training, she devised a simple apparatus to quantify the area covered by the oil film. Her apparatus was refined by Langmuir (1917) and is now generally referred to as a Langmuir trough (Figure 2), although it really should be a Pockels trough."

So that's it. Whole cellular biology science is based on this experiment done in the kitchen 100 years ago. Intrigued already?

Then see this.

In other words, CDC, first in front line of the battle with COVID thinks viruses are alive and eat protein. As for the formaldehyde part, i'm trying to think. Don't know of anything toxic inside a coronavirus.

Anyways this is not the purpose of this post. I'm still at the bylayer. Both cells and viruses are surrounded by a bylayer membrane. So when the viruses multiply inside a host cell in the end they have to "steal" a part of the cell's membrane to make it their own.

But then i realized i don't know how during cellular division (not all cells divide but most do) the "parent" cell shares its membrane to the two daughters.

What do i know. It looks like cells have muscles (and skeletons).
Actin and myosin. The muscle proteins inside cell that form the contractile ring that initiates the change of shape from spherical into two lobes and then the cell becomes two.

However virus progenies employ a different mechanism for generating their membrane. I was reading this article but did not fully understand how.

"Although membrane fusion for entry is a speciality of the enveloped viruses due to the presence of a lipid bilayer around them, HSV is capable of exploiting other routes of entry as well"

So we know how the virus enters the host cell. Membrane (lipid bylayer) fusion and/or endocytosis. But how is it released?

Apparently the virus emerges encapsulated by using parts of the Golgi network that turn into "secretory vesicles". But where the virus gets its spike proteins and how it breaks the cells membrane to escape?

I'm not getting to any conclusion yet and plan to read further in the immediate future but from what i read so far to me viruses are so fragile and the mechanisms of cell invasion, replication and building are so complicated it should take very little to brake them. Of course main motivation for writing this is frustration with a science and scientists who failed for such a long time to find something to disrupt them.

Prokaryote, Eukaryote. Lving Cells and Viruses

Anybody done with trusting scientists who for decades did not produce anything new in medicine? 500 billion a year payed by the US government in grants, for what? They give each other grades and honors, go to conferences, dress nicely, live the life but nothing has really progressed. All we got is theories that we believe are true. Some of them are and some, amazingly contradict or have never been harmonized to each other.

Last major discovery in medicine, antibiotics, has been done by chance. Good thing there was a guy who realized what happened in his Petri dish, when a fungus killed his cultures. That was 98 years ago. However political considerations did not allow mass production until after WWII. Imagine the number of lives that could have been saved during that war.

Vaccinations have has also been done way before modern medicine. At least in this book history of vaccination begins with 7th century India. But who can know for sure. Though i bet it started as an alchemical experiment (like curing fire with fire or whatever).

So here i go. I cannot afford the luxury to study first and write later because of lack of time and vastness of subjects. And because of that i usually start with an idea on a hunch and then run into something else. Like in the other post about lipid bilayer. Never finished the subject because i ran into the striking similarity between HIV and the so called COVID virus, the current scare. Something i did not expect. And then i started to suspect that like in seismology and other sciences, there might be massive lies and cover-ups and nothing solid under the glossy layer of publications and prizes and titles.

Most molecules, including water, are said to be... bipolar. Just kidding. They are just polar. Better said, asymmetrical. I mean, they can be bipolar but most of the times are multi-polar and sometimes even unipolar. Both electrical and mechanical. That is mass and electric charge is distributed spatially. At some ends charges are mostly positive and at some ends are negative. Same with weight. Water by example

Everybody knows if not from Paula Abdul song, the opposites attract, and for this reason only, in stationary water molecules arrange in matrix like structures. These intermolecular forces are rather weak. However they exist and play a very important role in everything we know. Most interesting at the separation between a liquid and a gas, they help create a membrane, because liquid molecules cling to each other (each end to other's opposite end). Capilarity. The reason textile fibers "get wet". For this reason in (absence of gravity) the drops of water are round or even exist. Some substances repel water. It is said they are hydrophobes. Water does not mix with oil, etc..

And here i am. Oil. What is oil made of. Fatty acids are not polar and for that reason they do not mix with water like it is said even in the Bible.

Phospholipids are fatty acids at one end and a phosphate group at the other. The are polar but only at one end (does this make sense to anyone) and still do not mix with water. Their phosphate heads would want to dissolve in water however their fatty tails do not. So they cling to each other forming a natural bilayer.

No matter what. If you throw some phospholipids (by the chemical formula above) in the water, you'll get a bilayer. For some reason that is within the same terms above, the phospolipids bilayers in water close in spheres like water drops in air though empty inside. Chemists call those micelles.

So from the beginning we had bipolarity, phobia, attraction and as we'll see later, some cannibalism. I can see now how confusing is for scientists to deal with all these.

It's no secret by now. All living things are made of these. It's also how it all started. Bilayers.

Everywhere i went to read about, it's a big dilemma. I mean, nowadays we have lipids, fatty acids, everywhere because they are synthesized by the living cells. Back then? Where they came from? To form the first micelle that is. That in billions of years got populated with DNA, ribosomes, all the good things that make a true cell which can divide and multiply.

In the beginning or 4 billion years ago they were only prokariotes. I bet it's a greek word. Nevermind that. Then it came eukariotes, 2 billions later. In the early 90s the old prokariotes were separated in two groups. Bacteria and archaea. These are the oldest living things on earth. They can be only unicellular. That is they do not combine with other of their kind to make an organism. And then, 2 billion years ago a bacteria ate another of its kind and did not digest it but the prey became the first nucleus of an newly created cell. The first eukariote. Or so they say.

And since we have such a neat distinction between the only two existing types of living cells, we can study them by comparison.

First. Eukariotes have a nucleus to keep their DNA togehter (DNA inside nucleus on left, the only thing not shown in this picture. Also not named the detailed components of the membrane and the peptidoglycan strata on the right).

Eukaryotes are much more evolved. They have by example mitochondria, an organelle that produces energy for the rest of the cell. Ribosome for synthesizing proteins. (Though a bit confusing. What do they mean by orders?) A bunch of other stuff. They evolved to make the multicelullar organisms we know today as plants or animals. But they can't live by themselves. That is they need to be fed with nutrients, oxygen and get rid of waste products, like carbon dioxide, urea, name it. However, they have the original bilayer while the prokariotes have more strata of membranes. That is because the prokariotes, or todays bacteria, live by themselves while the eukariotes within an extracellular matrix. Be it of cellulose, like in plants, or collagen like in animals. In the picture, plant cells in their cellulose matrix, from the same article in Live Science.
Viruses. Viruses are not living things. That is they cannot reproduce or perform any cell's function. They just sit there and wait to get inside a cell where they can make copies of themselves and in the process destroying that cell and that's it. They have though the same bilayer membrane of the eukariotes cells. Otherwise they could not merge with them, to implant their RNA inside the infected cell, from where many copies of the virus will emerge, probably using pieces of the bilayer of the host cell in the final assembly.

Never heard of a virus attacking a bacteria, because they have a much thicker membrane. What do you know... They have special viruses which are encapsulated in protein that can attack bacteria.

Since i mentioned penicillin. I think heard it before, wanted to see it one more time. Penicillin bursts bacteria's wall. That is the peptidoglycans part of the more structured bacterial (prokaryotes) wall. That BTW includes a bylipid component. It is understood. If you destroy the peptidoglycans, bylipid doesn't even matter. The bacteria cannot survive. Because it does not live inside the Extra Cellular Matrix. The reason penicillin does not kill all the cells in your body is because they don't have a peptidoglycan cell wall.  What?

Question. How the  coronavirus with its fragile bilayer only as membrane gets through the ECM (Ectra Celullar Matrix) to reach inside an eukariote cell?

There is only one answer to this. Only if the ECM is damaged exposing the cells. However, if this would happen the cells without the strong membrane of an autonomous prokaryote, would immediately fall apart. Or maybe the eukariote falls from its matrix inside blood stream and it's only there the virus attacks.

Got a bit tired. Need to re-read and continue.

Lipid Bilayer and (Corona) Virus Spikes

Had an idea and was trying to take a glimpse into cellular biology today. It all started with this type of media articles.

«Under the microscope [electron], coronaviruses appear to be covered with pointy spires, giving them the appearance of having a crown or "corona" -- hence the name. Beneath the crown is the outer layer of the virus, which is made up of lipids, or what you and I would call fat.»

There's something in there that doesn't really click my intuition.

Cells are said to be made of cytoplasm (a gel made 80% of water and other stuff floating in it) covered by fatty membranes. Please note the same type of membrane is shared by cells, bacteria and viruses.

It doesn't look to me like they have any mechanical resistance at all. I mean, bubbles of water based gel surrounded by a double molecule layer of fat.

If i didn't know about extracellular matrix which is made of collagen i'd say the body tissues can't even stay together.

Collagen is a protein that forms 30% of our bodies. To have an idea of how strong this stuff, is, enough to say tendons which are terminations of muscles through which they are attached to bones are made of collagen. If you make a fist you can see and feel them above the wrists of your hands.

By contrast "The cell membranes of almost all organisms and many viruses are made of a lipid bilayer, as are the nuclear membrane surrounding the cell nucleus, and other membranes surrounding sub-cellular structures. The lipid bi-layer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be."

First. We may note in this definition again viruses are separated from living organisms. Then. This lipid barrier separate the chemicals from inside the cells by those from outside. What's keeping it together is electrical bonds between molecules of lipid barrier mentioned above with absolutely no mechanical resistance. If it wasn't for extracellular matrix, those things would probably burst like a soap bubble and fall apart.



And my thought went of course to types of cells that "live" outside a cellular matrix. First thing that came to mind is red blood cells. So i looked and to my surprise i saw they lack a nucleus. "The cytoplasm of erythrocytes is rich in hemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the red color of the cells and the blood. ... The cell membrane is composed of proteins and lipids, and this structure provides properties essential for physiological cell function such as deformability and stability" So the natural question comes to mind. Are they alive? and of course that Quora answer didn't clarify anything. And on a further search i could not find an answer to the question if they use oxygen for themselves. Why should they. They don't need to burn oxygen to keep the temperature constant because rest of the body does that from them. I think the're more like molecular assemblies than living cells. Of course they wear out and "die" after a number of cycles of oxygen and carbon dioxide carrying.

Viruses. Their membrane is again made of a lipid bylayer. They of course don't have a nucleus because the're not cells though inside they have RNA which is part of the nucleus of living, reproducing cells.

Though they are not alive and obviously can't reproduce, once they entered a host cell they can "command" that cell to produce copies of themselves which sometimes are not "exact copies" and thus they... mutate. Some of the mutants will do less, some more than their "parents". The most complicated "component" the host cell needs to "fabricate" using the viral RNA instructions is the spike protein. In fact, the company who mapped this protein and can produce them uses viral RNA (linked later in this post).

I would assume they didn't provide the Jsmol model for the molecule, but here, for comparison, the molecule of HIV spike. If you click on "cartoon" on style for display option you will see the ribbon model. To compare size with lipid by-layer choose ball and stick.

We've saw so far seen the HIV virus looks identical (at least in some media representations) with coronaviruses. Part of the answer is... they are very similar. But the coronavirus misses something. The second membrane layer or the "matrix protein" seen in HIV of which the spikes are seemed to be anchored to.


There are other diagrams of coronaviruses on the web. They all suggest the "envelope" of the virus is made mostly of fat that includes some proteins.
Other, more scholarly articles, trying to suggests that the envelope of such viruses is made more of proteins than lipids. Or even lipids and unevenly distributed protein.

"We present evidence that suggests M can adopt two conformations and that membrane curvature is regulated by one M conformer. Elongated M protein is associated with rigidity, clusters of spikes and a relatively narrow range of membrane curvature. In contrast, compact M protein is associated with flexibility and low spike density."

"CoV virions are enveloped and consist of four structural proteins (Figure 1b). The RNA genome is encapsidated by the N proteins into a helical nucleocapsid, surrounded by a lipid envelope. Two major glycoproteins, M protein, which has three transmembrane (TM) domains, and S protein, which has a single TM domain; and minor non-glycosylated E proteins with a single hydrophobic domain, are incorporated into the CoV envelope"

By looking at the section (c) of the image below, i try to imagine what is the role of M (from Membrane) and E (from envelope) proteins in the envelope of the virus. Are they tied together in a structure or just caught loose in the fat (lipid) membrane.

US National Library of Medicine National Institutes of Health

"However, a recent electron microscopy study did not detect a well-ordered rigid lattice structure in individual virions, showing instead loosely ordered M-M protein networks [101], suggesting that the lattice-like matrix structure formed by M-M interactions might be flexible and unstable, and so that the model might need some modifications."

By looking at the animated image of the bylayer above and that of the spike protein and the two diagrams from Wikipedia here comes my question. How the gigantic spikes molecule hold onto the loose layer of thin fat (after neglecting the more obvious question that is how corona viruses which are basically a round bubble of fat with RNA inside and spikes outside hold themselves together inside blood). Can't figure yet the size of this protein but is should be certainly 100 times bigger than the two layers of fat acids figured above. Each straight portion of those "ribbons" below is probably as long as half of the thickness of the membrane.

So imagine that. A nanometric blob of fat with some genetic material inside flowing in the air from a sick person nearby getting into your lungs and attacking your cell. That is if your lungs' cilia and mucus don't eliminated them in your esophagus.

But what type of cells this "viruses" "attack" or "attach to"?

«"We then analyzed a total of nearly 60,000 cells to determine whether they activated the gene for the receptor and potential cofactors, thus in principle allowing them to be infected by the coronavirus," reports Soeren Lukassen, one of the lead authors of the study now being published in The EMBO Journal. "We only found the gene transcripts for ACE2 and for the cofactor TMPRSS2 in very few cells, and only in very small numbers." Lukassen and his four co-lead authors Robert Lorenz Chua, Timo Trefzer, Nicolas C. Kahn and Marc A. Schneider discovered that certain progenitor cells in the bronchi are mainly responsible for producing the coronavirus receptors. These progenitor cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs. Lukassen and his four co-lead authors Robert Lorenz Chua, Timo Trefzer, Nicolas C. Kahn and Marc A. Schneider discovered that certain progenitor cells in the bronchi are mainly responsible for producing the coronavirus receptors. These progenitor cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs."»

https://www.sciencedaily.com/releases/2020/04/200407131453.htm

But i bet no "virus" is going to attack you if those types of tissues wouldn't be already damaged. As i said above, most of your body's cells are protected by the strong collagen extracellular matrix through which a fat cover virus cannot possibly get through.

Pollutants, of which smoke is one of the worse factors. Smoke is a very complex compound of air born breathable substances of which the worse by far are heavy metals in ash, which can mutate bacteria creating unknown strain to your immune system, and also damage your respiratory tract lining cells.

In fact, the masks people are wearing to protect themselves from "virus" in fact protect them from the pollutants that may damage their respiratory tracts enough to make them vulnerable for infections because viruses are so small they will pass through most filters, not talking about masks.

As for the vaccine:

"The molecule the team produced – and for which they obtained a structure – represents only the extracellular portion of the spike protein, but is enough to elicit an immune response in patients."

And another question that becomes obvious after all this presentation. Can current HIV medicines be effective against coronavirus, since they are so similar?

"There are many newspaper articles citing effectiveness of anti-HIV drugs: ritonavir, lopinavir, either alone or in combination with oseltamivir, remdesivir, and chloroquine; and among these, ritonavir, remdesivir, and chloroquine showed efficacy at cellular level"

And since i put the two diagrams together to show the similarities with HIV virus, i started asking myself. How come they got flu vaccines which target the spikes ("the stems of the lollipop"), for so long and they don't have one for HIV.

"Doing that would require changing how the vaccine attacks the flu virus, which is shaped like a sphere with lollipops protruding from it. Vaccines so far have targeted the candy at the end of the lollipop, which changes every year."

The answer lies somewhere within the amount of money the drug companies get from insurance companies for a long life time supply of expensive antiviral drugs instead of a one time vaccine.