New research explains the active role that cilia have in ensuring certain bacteria are kept out of an organism while other symbiotic bacteria are selectively permitted to enter. The work was published earlier this week in Proceedings of the National Academy of Sciences from researchers at the University of Southern California Viterbi School of Engineering, Pacific Biosciences Research Center, the University of Hawaii at Manoa, and Stanford University.
The study describes a framework for the role of fluid mechanics in letting symbiotic bacteria into an organism and enhancing chemical communication between the symbiont and the host organism. The results are contrary to previous research, which assumes that cilia solely play a "clearance function."
To learn about how cilia might work in the human body, researchers examined how bobtail squids in their nascent stage allow symbiotic bacteria Vibrio fischeri to enter into their ciliated light organs. The scholars sought to know: why does this bacterium gain access and why do all bacteria fail to accumulate within the squid's light organ? In addition, they sought to explain what, if any, is the role of cilia in allowing access?
The researchers started with putting the squid under a microscope that then exposing it to water containing Vibrio fischeri bacteria. The process mimicked what happens in nature: the bacteria ended up in the correct spot within the squids' light organs. To find out if the cilia were passive or active during this process, the researchers repeated the same experiment, but with particles of the size as the bacteria. They found that the particles accumulated in the same spot, which demonstrated that a physical mechanism in the host (the squid) was at play. Next, they tried including larger particles and they did not have a greater probability of contact with the light organ. This indicated that direct interception was not the dominant mechanism for particle capture and that some other factor was at play.
After further investigation, Eva Kanso, Ph.D., a professor of mechanical engineering at USC Viterbi School of Engineering, and Janna Nawroth Ph.D., a principal investigator at Emulate, discovered that a "vortex-like" or "donut-like" flow generated by the cilia was kicking away most particles. The role of the fluid motion in filtering particles by size was verified using a physics-based mathematical model developed by Kanso and Guo, a Ph.D. student in Kanso's lab at USC. Kanso describes the role that cilia seemed to be playing as a "mechanical gate."
The researchers then mapped out the ciliated surface of the whole light organ and the flow field it generates. One of the core findings was that there were two distinct flows taking place by two different types of cilia. Longer cilia move in a "wave-like" fashion, which creates a "vortex-like" flow field that filters particles and then shorter cilia, which beat randomly keep the particles in place and gently mix the local flow. This random motion by the cilia and fluid mixing enhance the chemical screening of bacteria. To further prove the important role played by cilia, the researchers also found that if cilia are "killed," particles will accumulate everywhere in the organism.
The researchers are now developing a microfluidic platform to test the response of Vibrio fischeri to distinct flow and chemical signals presented by the ciliated light organ of the host.
Caption: The squid's internal light organ features several different populations of cilia (green/blue) that coordinate their beating activity to recruit symbiont bacteria from the seawater and facilitate their migration to the pores (right side), where they enter the organ for life-long colonization. Image courtesy of the lab of Margaret McFall-Ngai, Pacific Biosciences Research Center at the University of Hawaii.