Each of the
cells that make up
life are several orders of magnitude
smaller than a grain of salt. The sophisticated and complicated molecular activity that enables them to
perform the duties necessary for life to exist is hidden by their outwardly
simple-looking shapes. Researchers are starting to have a detailed
understanding of this behavior that they have never had before.
It is possible to envision biological structures either by beginning at the
level of the entire organism and working down, or by beginning at the level
of a single atom and working up. The cytoskeleton, which supports the form
of a cell, is one of its tiniest structures, while the ribosomes, which
produce proteins in cells, are one of its largest structures. However, there
has been a resolution gap between these two types of cell structures.
Using Google Maps as an example, scientists have been able to visualize
entire cities and individual homes, but they lacked the skills to understand
how the homes interacted to form communities. Understanding how different
parts interact in a cell's surroundings requires being able to see these
neighborhood-level features.
This gap is being gradually closed by new tools.
Cryo-electron tomography, or cryo-ET, is a unique technology that is still being developed, and it has the
potential to help researchers better understand how cells work in both
health and sickness.
I have seen amazing progress in the creation of instruments that can
identify biological structures in detail as a researcher who has researched
difficult-to-visualize big protein structures for decades and as the former
editor-in-chief of Science magazine. Understanding how biological components
fit together in a cell is crucial to comprehending how organisms function,
just as it becomes simpler to comprehend how complex systems work when you
are aware of what they look like.
An overview of microscopy's history
Cells were initially discovered using light microscopy in the 17th century.
In the 20th century, electron microscopy provided even more information,
exposing the complex internal organelles of cells, such as the endoplasmic
reticulum, a network of intricate membranes that is essential for protein
production and transport.
Biochemists sought to dissect cells into their molecular constituents
during the 1940s and 1960s. They also learned how to identify the 3D
structures of proteins and other macromolecules at or close to atomic
precision. To first see the structure of myoglobin, a protein that provides
oxygen to muscles, X-ray crystallography was used.
The quantity and complexity of the structures that scientists can see have
expanded significantly over the past ten years thanks to methods based on
nuclear magnetic resonance and cryo-electron microscopy, which create
pictures based on how atoms interact in a magnetic field.
Cryo-EM and Cryo-ET: what are they?
Cryo-electron microscopy, often known as cryo-EM, employs a camera to
record how an electron beam is bent as it travels through a sample in order
to see molecular structures. In order to shield samples from radiation
damage, they are quickly frozen. A 3D structure is created by averaging
numerous photographs of individual molecules to create detailed
representations of the target structure.
Cryo-ET and cryo-EM both employ comparable components, although they
operate in distinct ways. A area of interest within a cell is first thinned
using an ion beam since the majority of cells are too thick to be
photographed clearly. Similar to a CT scan of a bodily component, the sample
is then tilted to obtain several images of it at various angles. However, in
this instance, the imaging equipment itself is tilted, not the patient. A
computer then combines these photos to create a 3D representation of a
section of the cell.
Researchers or computer programs can use this image's great resolution to
distinguish the individual parts of various cell formations. This method has
been used by researchers, for instance, to demonstrate how proteins migrate
and break down inside an algal cell.
Researchers can now detect novel structures at much quicker speeds because
to the automation of several formerly manual methods used to assess the
architectures of cells. For instance, integrating cryo-EM with artificial
intelligence tools like AlphaFold can simplify picture interpretation by
foretelling as-yet-uncharacterized protein structures.
knowledge of cellular structure and operation
Researchers will be able to approach certain important topics in cell
biology in alternative ways as imaging techniques and procedures
advance.
Choosing which cells and which sections within those cells to research is
the first step. Fluorescent tags are used in conjunction with correlated light and electron microscopy, or CLEM, to find areas in live cells where
intriguing activities are occurring.
Comparing the genetic variations between cells can offer further
information. Cells that are unable to perform specific activities can be
examined by scientists to understand how this is reflected in their
structure. Researchers may analyze how cells interact with one another using
this methodology.
For some years, cryo-ET is likely to remain a specialist instrument.
However, as technology progresses and becomes more widely available, the
scientific community will be able to explore the relationship between
cellular structure and function at hitherto unattainable levels of detail. I
foresee new ideas advancing our understanding of cells from chaotic sacks of
molecules to delicately dynamic systems.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
