A field of stars glimpsed through a nebula? No, these constellations are extracellular vesicles, tiny packages carrying molecular cargo between cells.
We adjust a lens, and a bright constellation swirls into view – points of colored light hung against a deep-hued backdrop. We track them in their courses, their paths arcing around other, larger objects. Though the images look cosmic, they represent a frontier much tinier and closer to home. The glimmering stars are extracellular vesicles: tiny packages of molecular cargo in nanosized lipid carriers, released by all cells in the body.
Scientists once believed these vesicles were released to remove debris and waste from the cells. We now understand that EVs are readily absorbed by nearby cells, serving as an effective means of cell-to-cell communication, much like how hormones and nerves transmit messages throughout the body.
In most cases, EVs ensure proper health. However, they also can propagate disease. The most common example is in cancer, where a transformed tumor cell can release EVs that then pass to nearby cells to condition them for later metastases.
A stream of extracellular vesicles travels through blood vessels near a tumor.
Despite their importance in the body, we currently know very little about how EVs are released, trafficked, transported and distributed, or how they are taken up by cells – possibly at pre-determined locations. Current scientific methods capture only static 2-D snapshots of these biological processes and the attempts to piece together the dynamics. It’s like viewing a single frame from a full-length 3-D IMAX movie, then trying to infer all the characters, their personalities and motives, the setting and plot, and the denouement and final outcome of the entire story from that frame.
We’ve developed a novel way of imaging EVs label-free and in vivo – while they are still in the fluids, tissues or body. With real-time 3-D imaging, we can reveal the full story of the action, drama, romance, thriller, horror and comedy that is taking place in our biological systems every moment of the day.
We are launching a new project with the goal of not only visualizing EVs in living tissue, but also tracking their dynamics. We have been named 2023 Allen Distinguished Investigators by the Paul G. Allen Family Foundation for this purpose.
We are using a new microscope that collects optical signals we induce by shining light onto the tissue. The microscope is housed at the Beckman Institute for Advanced Science and Technology as a collaboration between the Molecular Muscle Physiology Lab and the Biophotonics Imaging Lab.
Importantly, we can visualize the EVs where they are located within a tissue, such as near blood vessels or emerging from specific cell types such as tumor cells. The optical signals we collect from the EVs also can tell us properties of the parent cells that produced them, such as the metabolic activity happening within those cells.
The microscope uses only special wavelengths of light, with no dyes or stains. Data from multiple wavelengths can be combined to give a full picture of the properties of tissues, cells and the vesicles traveling between them.
Our ability to capture all these dynamics without the use of labels, dyes or stains is also notable, because any of those can directly affect or perturb the very biological processes we are trying to study.
In our new roles as Allen Distinguished Investigators, we are focusing on how EVs are involved in the process of aging. Aging does not occur in just a few cells or one tissue at a time, but occurs in a systemic manner. We believe that EVs secreted from senescent cells, or cells in a permanent state of cell cycle arrest, circulate in the body and propagate the aging process.
The ability to visualize and characterize EVs over their lifespan, in real time, provides a window into the aging process. Perhaps this understanding could even lead to developing therapies to slow the aging process. We are thrilled to be at the forefront of answering some of these questions.
As Allen Distinguished Investigators, the Bopparts will follow vesicles over their lifespan to determine their role in the aging process.