Tag Archives: matrix

The extracellular matrix, and how it keeps you in tip top shape

Would you live in a city without streets? Or in a flat with no walls? Probably not — and the cells in our bodies expect the same level of comfort. Today, we’re taking a look at the tissues that create and maintain an ideal working environment for our tissues: the extracellular matrix.

A mammalian trachea cross-section, magnified 200 times.
Image credits Berkshire Community College Bioscience Image Library / Flickr.

We’ve had a look at the differences between animal and plant cells before (here’s a refresher). One of the key differences between them is that plants reinforce their cells with thick, sturdy walls. These walls are why plant tissues such as wood can get so resilient. However, the reverse of the coin is that it also limits plant cells somewhat: a muscle made out of wood wouldn’t be very effective.

Animals need cells that can perform a wide variety of activities, but these cells also need biological and mechanical support to perform their tasks. That’s where the extracellular matrix, or “ECM”, comes in.

So what is it?

The ECM is a complex mix of proteins and carbohydrates that fills the spaces between cells; it is comprised of the basement membrane and interstitial matrix. Going forward, I’ll use the term ECM quite loosely to mean both ‘the extracellular matrix’ and ‘the interstitial matrix’. If I don’t mention the basement membrane specifically, I’m probably talking about the interstitial matrix (as it’s the more dynamic and frankly more interesting half of the topic).

Think of the basement membrane as a sheet of plastic wrap the body stretches over every individual tissue or organ to keep everything tidy and in place. This membrane is made up of two layers of cells and it’s quite fibrous and hard to rip.

X-ray of an elbow. The ECM in our joints (the empty volume between the bones) uses more collagen to become tough and resistant to wear.
Image via Wikimedia.

The interstitial matrix is, for lack of a better term, the goo that our cells live in. Most of the time, it looks and feels a bit like a clear gel. It’s produced by the cells themselves, which secrete and release certain compounds around them.

The simplest definition of the extracellular matrix is that it represents the sum of non-cellular components present within all tissues and organs. As we go forward, keep in mind that the ECM isn’t the same everywhere.

What’s it made of?

“Although, fundamentally, the ECM is composed of water, proteins, and polysaccharides, each tissue has an ECM with a unique composition and topology that is generated during tissue development,” Christian Frantz, Kathleen M. Stewart, Valerie M. Weaver, 2010.

Collagen, the most abundant protein in mammals, is the main component of the ECM. Outside the cell, collagen binds with carbohydrate molecules and assembles into long molecules called collagen fibrils. These fibrils extend through the ECM and lend flexibility and strength to the material, acting similarly to the role of rebar in reinforcing concrete (which is tough but inflexible). Collagen fibrils are flexible and tough to break, so they’re used to ‘bind together’ the rest of the ECM. In humans, genetic disorders that affect collagen (such as Ehlers-Danlos syndrome) cause tissues to become fragile and tear easily.

While the ECM contains a wide range of proteins and carbohydrates, another important set of compounds alongside collagen are proteoglycans (groups of proteins tied to simple sugars). Proteoglycans come with many shapes and functions, depending on which proteins and sugars they’re made of, and perform a wide range of tasks in the ECM. They can also bind to each other, to collagen (forming cartilage), or to hyaluronic acid, making them even more versatile. As a rule of thumb, proteoglycans act as fillers and regulate the movement of molecules through the ECM among other functions.

Collagen fibers in rabbit skin.
Image via Wikimedia.

Their overall structure looks like a tree: the ‘sugar’ part of the polyglycans are twigs set on a branch (the protein), which ties to a trunk made out of polysaccharide (‘many-sugar’) molecules. A class of proteins in the membranes of cells, called integrins, serve as connection ports between the membrane and material in the ECM (such as collagen fibers and proteoglycan-polysaccharide bundles). Beneath the membrane, integrins tie into the cell’s support ‘girders’ (the cytoskeleton).

The type of ECM I’ve described so far is your run of the mill variety that you’ll find in skin, around muscle fibers, in adipose tissue (fat), and so on. But each tissue has an ECM that fully supports its function — blood plasma is the interstitial matrix of blood. Unlike the ECM of muscles, for example, which is meant to reduce friction and wear in the tissue, blood plasma primarily works as a medium to carry blood cells around. Blood vessels are coated with a basement membrane, and together, they form the ECM of blood. Each type of animal connective tissue has its own type of ECM, even bone.

What does it do?

Cross-section of compact human bone, magnified 100 times.
Image credits Berkshire Community College Bioscience Image Library / Flickr.

Seeing as there are many types of ECM out there, it stands to reason that there are many functions they perform. However, by and large, there are a few functions that all ECMs fulfill.

The first and perhaps most important function is that they provide support to tissues, segregate (separate) them, and that they mediate intercellular communication. The ECM is also what regulates a cell’s ‘dynamic behavior’ — i.e. whether a cell moves around, and how. The ECM keeps cells in place so we don’t simply unravel. The connections formed between the ECM and integrins on a cell’s membrane also function as signaling pathways.

It is also essential for the good functioning of tissues at large. The ECM creates and maintains the proper environmental conditions for cells to develop, multiply, and form functioning tissues. While the exact details are still unknown, the ECM has been found to cause tissue regrowth and healing after injury. In human fetuses, for example, the extracellular matrix works with stem cells to grow and regrow all parts of the human body. Fetuses can regrow anything that gets damaged in the womb, but since babies can’t, we suspect that the matrix loses this function after full development. Researchers are looking into applying it for tissue regeneration in adults.

The ECM can also act as a storage space for various compounds. In joints, it contains more hyaluronic acid which in turn absorbs water and acts as a mechanical cushion. ECMs can also store a wide range of cellular growth factors and release them as needed. This allows our bodies to activate cell growth on a dime when needed without having to produce and ship these factors to a certain area.

It also seems to impact cell differentiation and gene expression. Cells can switch genes on or off depending on the elasticity of the ECM around them. Cells also seem to want to migrate towards stiffer areas of the ECM generally (durotaxis) from less-firm ones.

The ECM isn’t very well known today, and it definitely goes unsung. But no matter how you cut it, it is a key part of biology as we know it today. Without it, both animals and plants would be formless, messy blobs — quite literally. And I don’t know about you but I love it when my tissues stay where they’re supposed to, the way they’re supposed to.


We’re one step closer to fully-functioning artificial blood vessels

A new study describes how researchers 3D-printed fully-functional blood vessels, and how they can be implanted into living hosts.

Blood vessel with a reduced cross-sectional area.
Image via Wikimedia.

The blood vessels were printed from a bioink containing human smooth muscle cells (harvested from an aorta) and endothelial (lining) cells from an umbilical vein. They have the same dual-layer architecture of natural blood vessels and outperform existing engineered tissues, the team explains.

The findings bring us closer to 3D-printed artificial blood vessels that can be used as grafts in clinical use.

Bloody constructs

“The artificial blood vessel is an essential tool to save patients suffering from cardiovascular disease,” said lead author Ge Gao. “There are products in clinical use made from polymers, but they don’t have living cells and vascular functions.”

“We wanted to tissue-engineer a living, functional blood vessel graft.”

The researchers explain that the small-diameter blood vessels we’ve been able to construct so far were fragile things, and prone to blockages. The crux of the issue was that these vessels relied on a very simplified version of the extracellular matrix — the material between cells which keeps our bodies together — most usually in the form of collagen-based bioinks. A natural blood vessel, however, isn’t just collagen; it also boasts a wide range of biomolecules that support the growth and activity of vascular cells.

To address these issues, the team developed a bioink starting from native tissues that preserves this extracellular complexity. Its use allows for faster development of vascular tissues and results in blood vessels with better strength and anti-thrombosis (i.e. anti-clogging) function. After fabrication, the team matured the vessels in the lab to reach specific wall thickness, cellular alignment, burst pressure, tensile strength, and contraction ability — basically making the printed vessels mimic the functions of natural blood vessels.

Afterward, the printed blood vessels were grafted as abdominal aortas into six rats. Over the following six weeks, the rats’ fibroblasts (a type of cell in the extracellular matrix) formed a layer of connective tissue on the surface of the implants — which integrated the vessels into pre-existing living tissues.

The team says they plan to continue developing the process in order to make the blood vessels stronger, with the goal of making them similar to human coronary arteries in physical properties. They also want to perform a long-term evaluation of vascular grafts to see how they evolve as they integrate into the implanted environment.

The paper “Tissue-engineering of vascular grafts containing endothelium and smooth-muscle using triple-coaxial cell printing” has been published in the journal Applied Physics Reviews.

Reticular adhesions.

New structure that keeps cells bound together discovered in human cells

Researchers at the Karolinska Institutet, Sweden, report discovering a new structure in human cells. The role of this cellular structure protein seems to be fixing cells to surrounding tissues and aiding in division, the team reports.

Reticular adhesions.

Three-dimensional projection of a cancer cell that has been rounded to undergo cell division and adheres to the substrate with reticular adhesions. Blue – Chromatin (DNA); Red – Cell’s outer shell (membrane); Green/Yellow – Reticular adhesions. The image was created using a confocal microscope.
Image credits John Lock.

Cells are round-ish, soft-ish things. So then how do they tie together to form robust tissues? Well, the secret lies in a structure that surrounds them — a net-like formation known as the extracellular matrix. Much like the mortar in between bricks, this matrix brings cells together into a coherent whole.

Still, the matrix is an exclusive place — only those with special receptor molecules (adhesion complexes) on their surface are admitted. The structure discovered by the team is one such adhesion complex.

Yet more to discover

“It’s incredibly surprising that there’s a new cell structure left to discover in 2018,” says principal investigator Staffan Strömblad, professor at the Department of Biosciences and Nutrition at the Karolinska Institutet.

“The existence of this type of adhesion complex has completely passed us by.”

The team discovered a new type of protein complex that cells use to attach to their surroundings and plays a key part in cell division. Much like other adhesion complexes, it connects the outside to the cell interior and informs the cell about its immediate environment, affecting its properties and behavior. What’s special about this one is its unique molecular composition and shape — the team christened the structure ‘reticular adhesions’ to reflect their net-like shape.

While other known adhesion complexes break down during division, reticular adhesions remain intact and attached to the cell wall during the process. This discovery could help solve the long-standing question of how cells remain attached to the matrix as they divide. The team further reports that the new structure controls where daughter cells go after division, ensuring that they occupy the right place in the overall tissue.

“Our findings raise many new and important questions about the presence and function of these structures,” says Professor Strömblad. “We believe that they’re also involved in other processes than cell division, but this remains to be discovered.”

For the study, the team looked at human cell lines using confocal microscopy and mass spectrometry. To better understand the function of reticular adhesions, they add, further research efforts will need to examine them in living organisms.

Apart from the direct scientific merits of the discovery, the biggest takeaway (for me) from this research is that nature is way more complex and complicated than we give it credit for. We shouldn’t rest on our laurels because we’ve ‘discovered everything’ — we’re nowhere near done yet.

The paper “Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis” has been published in the journal Nature Cell Biology.

deja-vu-matrix

What causes Déjà vu — the unsettling feeling of familiarity in novel situations

Déjà vu, pronounced ‘day-zhaa voo’, is French for ‘already seen.’ It describes the eerie sensation of familiarity in a seemingly new setting and environment. For instance, you may have found yourself in the middle of a conversation thinking to yourself that this exact exchange has taken place before. Or you may have walked into a totally new environment, and said to yourself “I’ve been here before!”. It’s all strangely familiar, but you can’t quite wrap your mind around the whole thing. In a sense, it’s a bit like seeing into the future.

Déjà vu is commonly featured in pop culture. In the movie The Matrix, a déjà vu is usually a glitch in the Matrix —  a computer-generated dream world, built to keep us under control while a cybernetic organism farms our bodies. But despite most people (60-80%) reporting that they have experienced the unsettling feeling at least once in their lifetimes, déjà vu has been startling understudied. To researchers’ credit, the fleeting, uncontrollable nature of déjà vu has made it difficult to study.

Scientists have proposed various hypotheses for déjà vu formation in the brain. According to one theory, the phenomenon might arise due to some sort of “mismatch” in how we’re simultaneously sensing and perceiving the world around us. Another theory suggests that the brain may occasionally take a short-cut to long-term memory storage, bypassing short-term working memory, evoking the sensation that of experiencing something in the distant past. The mainstream line of thinking is that déjà vu is a product of false memories — glitches in our neural matrix.

“[Déjà vu] is certainly related to false memory in the sense that it is a memory dissociation kind of effect. It dissociates reality from your memory,” said Valerie F. Reyna, a psychologist and Professor of Human Development at Cornell University and an expert on false memory and risky decision making.

“There’s all kinds of different dissociative experiences that can happen. Sometimes you cannot be sure, for example, if you dreamed something or experienced it, if you saw it in a movie or it happened in real life.”

But in 2016, Akira O’Connor, a psychologist at the University of St. Andrews in Britain, found that the phenomenon might be the result of front regions of the brain ‘fact checking’ our memories and sending signals when it encounters a sort of error. This error generates a conflict between what we’ve actually experienced and what we think we’ve experienced. By this explanation, déjà vu represents a mechanism that ensures that we don’t form false memories, or at least keeps them to a minimum, and is not the product of false memories themselves. This may also explain why the phenomenon is far more common in younger people, since memory deteriorates with age.

“Déjà vu is characterized by having a false sensation of familiarity, alongside the awareness that that sense of familiarity cannot possibly be correct,” O’Connor said. “It’s a memory clash where there’s false familiarity, together with an objective awareness that it can’t be real.”

O’Connor and colleagues enlisted 21 volunteers, who each were exposed to a list of words related to sleep — such as bed, pillow, night, or dream — but not the keyword itself that links all of them together. The participants were then asked whether they had heard the word ‘sleep’. Those who responded affirmatively were then asked whether they had heard any word from the previous list start with the letter “s”, to which they responded negatively. The resulting confusion triggered déjà vu in two-thirds of participants.

The next step was to scan the brains of the participants with a functional magnetic resonance imaging (fMRI) machine to see which brain regions lit up when the experience took place.

“What we found was that it wasn’t memory-linked regions that are driving déjà vu,” he said. “Traditionally, researchers thought déjà vu was being driven by false memories. What it actually is is that the cognitive control, error-monitoring conflict-checking frontal brain regions are the ones which show greater activity in people reporting the experience.”

What does this mean for people who have never had déjà vu? Well, it may mean that these people don’t reflect on their memory system. On the other hand, people who don’t have déjà vu might simply have a better memory than the general population, so there’s no risk of triggering memory errors.

As to why people have déjà vu in the first place, the jury isn’t out yet. It may be an evolutionary product that makes people more cautious when memory is playing tricks on us, but there’s no evidence backing this idea up yet.

 

Three Old Scientific Concepts Getting a Modern Look

If you have a good look at some of the underlying concepts of modern science, you might notice that some of our current notions are rooted in old scientific thinking, some of which originated in ancient times. Some of today’s scientists have even reconsidered or revamped old scientific concepts. We’ve explored some of them below.

4 Elements of the Ancient Greeks vs 4 Phases of Matter

The ancient Greek philosopher and scholar Empedocles (495-430 BC) came up with the cosmogenic belief that all matter was made up of four principal elements: earth, water, air, and fire. He further speculated that these various elements or substances were able to be separated or reconstituted. According to Empedocles, these actions were a result of two forces. These forces were love, which worked to combine, and hate, which brought about a breaking down of the elements.

What scientists refer to as elements today have few similarities with the elements examined by the Greeks thousands of years ago. However, Empedocles’ proposed quadruplet of substances bares resemblance to what we call the four phases of matter: solid, liquid, gas, and plasma. The phases are the different forms or properties material substances can take.

Water in two states: liquid (including the clouds), and solid (ice). Image via Wikipedia.

Compare Empedocles’ substances to the modern phases of matter. “Earth” would be solid. The dirt on the ground is in a solid phase of matter. Next comes water which is a liquid; water is the most common liquid on Earth. Air, something which surrounds us constantly in our atmosphere, is a gaseous form of matter.

And lastly, we come to fire. Fire has fascinated human beings for time beyond history. Fire is similar to plasma in that both generate electromagnetic radiation such as light. Most flames you see in your everyday life are not hot enough to be considered plasma. They are typically considered gaseous. A prime example of an area where plasma is formed is the sun. The ancient four elements have an intriguing correspondent in modern science.

Ancient Concept of Dome Sky vs. Simulation Hypothesis

Millennia ago, people held the notion that his world was flat. Picture a horizontal cooking sheet with a transparent glass bowl set on top of it. Primitive people thought of the Earth in much the same way. They considered the land itself as flat and the sky as a dome. However, early Greek philosophers such as Pythagoras (c. 570-495 BC) — who is also known for formulating the Pythagorean theorem — understood that Earth was actually spherical.

Fast forward to the 21st century. Now scientists are considering the scientific concept of the dome once again but in a much more complex manner.

Regardless of what conspiracy lovers would have you believe, the human race has ventured into outer space, leaving the face of the Earth to travel to the stars. In the face of all our achievements, some scientists actually question if reality is real, a mindboggling and apparently laughable idea.

But some scientists have wondered if we could be existing in a computer simulation. The gap between science and science fiction starts to become very fine when considering this.

This idea calls to mind classic sci-fi plots such as those frequently played out in The Twilight Zone in which everything the characters take as real turns out to be something entirely unexpected. You might also remember the sequence in Men in Black in which the audience sees that the entire universe is inside an alien marble. Bill Nye even uses the dome as an example in discussing hypothetical virtual reality. This gives one the feeling that he is living in a snowglobe.

Medieval Alchemy vs. Modern Chemistry

The alchemists of the Middle Ages attempted to prove that matter could be transformed from one object into an entirely new object. One of their fondest goals they wished to achieve was the creation of gold from a less valuable substance. They were dreaming big, but such dreams have not yet come to fruition. Could it actually be possible to alter one type of matter into another?

Well, modern chemists may be well on their way to achieving this feat some day. They are pursuing the idea of converting light into matter, as is expressed in Albert Einstein’s famous equation. Since 2014, scientists have been claiming that such an operation would be quite feasible, especially with extant technology.

Einstein’s famous equation.

Light is made up of photons, and a contraption capable of performing the conversion has been dubbed “photon-photon collider.” Though we might not be able to transform matter into other matter in the near future, it looks like the light-to-matter transformation has a bright outlook.

Matrix

Novices learn faster after being zapped with expert brain wave patterns

In the movie, The Matrix, Neo masters over a dozen martial arts in a fraction of a second as the necessary skills are uploaded straight into his consciousness. Given our current understanding of how the brain works, this is quite preposterous in real life but you’ll be surprised to hear some scientists have tested a similar ‘skill upload’ system with remarkable results.

Matrix

Using  transcranial direct current stimulation, or TDCS for short, a team from Malibu-based HRL Information and System Sciences Laboratory transmitted the recorded brain patterns of six commercial airline pilots to novices learning to fly.

We know that when an expert and a novice attempt to perform the same task, their brain patterns will be different. Ever wondered how an expert makes a task look easy? All that grace and finesse is the product of thousands of hours of practice, which in the brain are captured in ‘neural superhighways’ which aren’t yet formed in the novice brain.

The novices received the zaps that encoded the expert brain wave patterns through electroencephalography (EEG) caps. Over a period of four consecutive days, the 32 participants went through standard flight training procedures like taking off, altitude control, controlled descent and so on, all with their thinking caps on.

During these exercises, some had brain wave patterns fired through the EEG cap, while others received mock simulations.

At the end of the trial, those who actually went through real TDCS performed better than those who didn’t — 33 percent better, the scientists report in  Frontiers in Human Neuroscience

Previously, researchers used similar neural modulation to enhance training for  concealed image detectionspatial and verbal working memorieslanguage acquisition or motor skills development.  All reported improved performance in training.

Note that while TDCS improved training, it still required active implication from behalf of the novices. In other words, there’s no knowledge transfer but a facilitation. It doesn’t seem like uploading martial arts brain wave patterns will make you into a Kung Fu master anytime soon, but the findings are still staggering considering this field is still in its infancy.

There are some critics that aren’t convinced, though. Science Alert has a roundup, noting sources that call this research “bogus”.

HRL Laboratories does R&D for the Boeing Company and General Motors, and have already filed a patent for their ‘brain-boosting’ interface, so the prospect of financial gain could have clouded the results, or their perception of the results.

Mark S. George, a professor of psychiatry, radiology, and neurosciences at the Medical University of South Carolina, and editor-in-chief of the science journalBrain Stimulation, told Gizmodo that the results are based on a “small sample study in vulnerable employees, performed by scientists with patents pending that will be influenced by the outcome”, adding that in the past, results from tDCS studies have failed to be replicated.