Think back to that basic biology class you took in high school. You probably learned about organellesthese small “organs” inside cells that form compartments with individual functions. For example, mitochondria produce energy, lysosomes process waste, and the nucleus stores DNA. Although each organelle has different functions, they are similar in that each is covered by a membrane.
Membrane-bound organelles were the textbook standard for how scientists thought cells were organized. until they realized in the mid-2000s that some organelles do not necessarily need to be wrapped in a membrane. Since then, researchers have discovered many additional membraneless organelles that have significantly changed the way biologists think about chemistry and the origins of life.
I was introduced to membraneless organelles, formally called biomolecular condensatesa couple of years ago, when students in my laboratory observed several unusual spots in the cell nucleus. Unbeknownst to me, we had been studying biomolecular condensates for many years. What I finally saw in these droplets opened my eyes to a whole new world of cell biology.
Like a lava lamp
To get an idea of what a biomolecular condensate looks like, imagine a lava lamp in which the wax droplets inside merge, break apart, and merge again. Condensates are formed in approximately the same wayalthough they are not made of wax. Instead, a cluster of proteins and genetic material, particularly RNA molecules, in the cell condense into gel-like droplets.
Some proteins and RNAs do this because they preferentially interact with each other rather than with their environment, much like the way drops of wax in a lava lamp mix with each other but not with the surrounding liquid. These condensates create a new microenvironment that attracts additional proteins and RNA molecules, thereby forming a unique biochemical compartment within the cells.
As of 2022, researchers have discovered approximately 30 types of these membraneless biomolecular condensates. By comparison, about a dozen traditional membrane-bound organelles are known.
While it's easy to identify if you know what you're looking for, it's difficult to know what exactly biomolecular condensates do. Some of them have clearly defined roles, such as forming reproductive cells, stress granules And ribosomes that make protein. However, many others do not have clear functions.
Non-membrane-bound organelles may have more numerous and varied functions than their membrane-bound counterparts. Studying these unknown functions impacts scientists' fundamental understanding of how cells work.
Protein structure and function
Biomolecular condensates challenge some long-held beliefs about protein chemistry.
Since scientists were first able to take a close look at myoglobin protein structure in the 1950s it became clear that its structure is important for the ability to carry oxygen to the muscles. Since then, the mantra of biochemists has been that protein structure equals protein function. Essentially, proteins have a specific shape that allows them to do their job.
Proteins that form biomolecular condensates, at least partially, violate this rule because they contain disordered regions, that is, they do not have a specific shape. When researchers discovered these so-called intrinsically disordered proteins, or IDPsIn the early 1980s, they were initially puzzled by how these proteins could not have a strong structure but still perform specific functions.
Later they discovered that IDPs tend to form condensates. As is often the case in science, this discovery resolved one mystery about the role of these unstructured rogue proteins in the cell, but opened up another deeper question about what biomolecular condensates actually are.
Bacterial cells
The researchers also found biomolecular condensates in prokaryotesor bacterial cells, which were traditionally considered to contain no organelles. This discovery could have a profound impact on how scientists understand the biology of prokaryotic cells.
Only about 6% bacterial proteins have disordered regions lacking structure, compared to 30–40% of eukaryotic or nonbacterial proteins. But scientists have discovered several biomolecular condensates in prokaryotic cells that are involved in various cellular functions. including production and RNA cleavage.
The presence of biomolecular condensates in bacterial cells means that these microbes are not simple packages of proteins and nucleic acids, but are in fact more complex than previously thought.
Origins of life
Biomolecular condensates are also changing scientists' views on the origins of life on Earth.
There is ample evidence that nucleotides, the building blocks of RNA and DNA, can plausibly be produced from common chemicals such as hydrogen cyanide and water, in the presence of common energy sources such as ultraviolet light or high temperatures, from common minerals such as silica and iron clay.
There is also evidence that individual nucleotides can spontaneously gather in chains to create RNA. This is a decisive step in RNA world hypothesiswhich postulates that the first “life forms” on Earth were strands of RNA.
The main question is how these RNA molecules could have evolved mechanisms to replicate and organize into a protocell. Since all known life is contained in membranes, researchers studying the origins of life have generally assumed that membranes must also encapsulate these RNAs. This will require the synthesis of lipids or fats that make up the membranes. However, the materials needed to produce lipids were likely not present on the early Earth.
With the discovery that RNAs can spontaneously form biomolecular condensates.lipids will not be necessary for the formation of protocells. If RNA could independently aggregate into biomolecular condensates, it would become even more plausible that living molecules arose from nonliving chemicals on Earth.
New treatments
It's exciting for me and other scientists studying biomolecular condensates to dream about how these rule-breaking creatures will change the way we think about how biology works. There are already condensates. changing the way we think about human diseases like Alzheimer's, Huntington's and Lou Gehrig's.
To this end, researchers are developing several new approaches to manipulate condensates for medical purposes as new drugs that can stimulate or dissolve condensates. Whether this new approach to treating diseases will bear fruit remains to be determined.
In the long term, I would not be surprised if each biomolecular condensate is eventually assigned a specific function. If that happens, you can bet that high school biology students will have even more to learn—or complain about—in their introductory biology classes.
This article has been republished from Talka nonprofit, independent news organization bringing you facts and trusted analysis to help you make sense of our complex world. He was written by: Allan Albig, Boise State University
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Allan Albig receives funding from the National Institutes of Health.
