Researchers at the Massachusetts Institute of Technology (MIT) have developed a revolutionary method enabling the observation of up to seven distinct molecules simultaneously within a living cell, with potential for even broader molecular insights.
The technique, utilizing fluorescent markers that alternate between active and inactive states, allows MIT scientists to examine the interactions of cellular molecules in detail, significantly contributing to our understanding of cellular behavior.
Cells, constantly receiving a variety of molecular signals, exhibit behaviors influenced by these inputs. By measuring these signals and the resulting cellular reactions within molecular signaling networks, researchers can gain deeper insights into cellular functions, aging processes, and disease mechanisms.
Current cell imaging methods are restricted to observing only a few molecular types simultaneously within a cell. The MIT team’s innovative approach overcomes this limitation, offering a more comprehensive view of molecular dynamics inside cells.
Pioneering Techniques in Molecular Imaging
Edward Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, emphasizes the importance of understanding the chain reactions in biological processes that lead to specific cellular functions. Their objective was to create a method to directly observe these processes.
This novel method involves the use of green or red fluorescent molecules that intermittently light up and fade. Over extended periods, these molecular changes are recorded and analyzed using computational algorithms, allowing for the tracking of protein quantities and their variations over time.
In one example, MIT researchers successfully labeled and imaged four different kinases within cells. Boyden, also a professor of biological engineering and brain and cognitive sciences at MIT, as well as a Howard Hughes Medical Institute investigator, led this study, published in the journal Cell on November 28. Yong Qian, an MIT postdoc, is the paper’s lead author.
Advancements in Fluorescent Signal Analysis
The practice of labeling cellular molecules with fluorescent proteins has significantly advanced our understanding of cellular functions. This method, often involving green fluorescent protein (GFP) since the 1990s, has expanded to include proteins glowing in various colors.
However, traditional light microscopes are limited to distinguishing only two or three colors, restricting the scope of observable cellular activity. With the ability to track more labeled molecules, researchers can explore complex cellular responses, such as a brain cell’s reaction to neurotransmitters or the mechanisms behind cancer metastasis.
Boyden’s lab previously developed a method for imaging up to five different molecules inside a cell using spatial multiplexing. The current study introduces a time-based approach, employing “switchable fluorophores”—fluorescent proteins that toggle on and off at specific rates.
This technique, akin to distinguishing different instrument sounds in an orchestra, uses a computational method called linear unmixing. This process is comparable to the Fourier transform, which separates different sound frequencies.
After analyzing the data, researchers can pinpoint the locations and timings of the fluorescently labeled molecules throughout the imaging period. Remarkably, this process only requires a standard light microscope.
Exploring Complex Biological Processes
In their study, the team demonstrated the method by labeling six molecules involved in cell division, revealing patterns in cyclin-dependent kinase levels throughout the cell cycle. They also labeled various kinases, cell structures, and organelles, proving the technique’s efficacy in mammalian cells and zebrafish larvae brains.
This approach holds promise for observing cellular responses to diverse stimuli, such as nutrients, immune factors, hormones, or neurotransmitters, and for studying gene expression changes and genetic mutations. These factors are crucial in understanding growth, aging, cancer, neurodegeneration, and memory formation.
Boyden’s team is further expanding their repertoire of switchable fluorophores and adapting the system for use in mouse models.
The study, titled “Temporally multiplexed imaging of dynamic signaling networks in living cells,” was funded by various sources, including the K. Lisa Yang Center for Molecular Therapeutics at MIT and the National Institutes of Health.
Frequently Asked Questions (FAQs) about Cellular Imaging Technology
What is the new cellular imaging technique developed by MIT?
MIT researchers have created a method that allows for the observation of up to seven different molecules simultaneously within a living cell. This technique uses fluorescent labels that switch on and off, enabling detailed study of how molecules interact and control cell behavior.
How does this new technique improve our understanding of cells?
The new imaging method provides a more comprehensive view of the interactions and behaviors of molecules within living cells. This can lead to better insights into cellular functions, the aging process, and disease mechanisms.
What makes MIT’s cellular imaging method unique?
The uniqueness of this method lies in its ability to observe multiple molecular types within a cell at the same time, surpassing the limitations of current imaging techniques that can only view a few molecules simultaneously.
What are the potential applications of this imaging technology?
This technology could be used to study a wide range of cellular responses and processes, including how cells react to different stimuli like nutrients or hormones, and how they change during growth, aging, cancer development, neurodegeneration, and memory formation.
Who led the research team for this study at MIT?
The research was led by Edward Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, who is also a professor of biological engineering and brain and cognitive sciences, and a Howard Hughes Medical Institute investigator.
More about Cellular Imaging Technology
- MIT News: Revolutionary Cellular Imaging Method
- Cell Journal: Study on Temporally Multiplexed Imaging
- Howard Hughes Medical Institute: Edward Boyden’s Research Profile
- MIT McGovern Institute for Brain Research: Advancements in Cellular Imaging Techniques