Most people are familiar with audiences in crowded arenas performing “the wave,” raising their hands in sync to produce a pattern that propagates around the whole stadium. This self-organized motion appears seemingly out of nowhere. It is not produced by any external control, but is rather emerges from thousands of individuals interacting only with their neighbors. A similar principle of self-organization might also be relevant on length scales that are billion times smaller. On this scale, nanometer-sized proteins interact with each other to produce dynamical structures and patterns that are essential for life—and some of these processes are reminiscent of waves in crowded stadiums. For example, thousands of nano-sized molecular motors located within a single eukaryotic flagellum or cilium coordinate their activity to produce wave-like beating patterns. Furthermore, dense arrays of cilia spontaneously synchronize their beating to produce metachronal waves.
Proper functioning of cilia is essential for health; for example, cilia determine the correct polarity and location of our organs during development. Defective cilia can cause a serious condition called situs inversus, in which the positions of the heart and lungs are mirrored from the normal state. In another example, thousands of cilia in our lungs function to clear airways of microscopic debris such as dust or smoke by organizing their beating into coordinated, wave-like patterns. Despite the importance of ciliar function, the exact mechanisms that lead to spontaneous wave-like patterns within isolated cilia, as well as in dense ciliary fields, is not well understood.
In a paper published in the journal Science this week, an interdisciplinary team consisting of physics graduate student Timothy Sanchez and biochemistry graduate student David Welch working with biophysicist Zvonimir Dogic and biologist Daniela Nicastro present a striking finding: the first example of a simple microscopic system that self-organizes to produce cilia-like beating patterns. Their experimental system consists of three main components: 1) microtubule filaments; 2) motor proteins called kinesin, which consume chemical fuel to move along microtubules; and (3) a bundling agent that induces assembly of filaments into bundles. Sanchez et al. found that under a certain set of conditions, these very simple components are able to self-organize into active bundles that spontaneously beat in a periodic manner. One large spontaneously beating bundle is featured below:
In addition to observing the beating of isolated bundles, the researchers were also able to assemble a dense field of bundles that spontaneously synchronized their beating patterns into traveling waves. An example of this higher-level organization is shown here:
The significance of these observations is several-fold. First, due to the importance of ciliar function for health, there is great interest in elucidating the mechanism that controls the beating patterns of isolated cilia as well as dense ciliary fields. However, the complexity of these structures presents a major challenge. Each eukaryotic flagellum and cilium contains more than 600 different proteins. For this reason, most previous studies of cilia and flagella have employed a top-down approach; they have attempted to elucidate the beating mechanism by deconstructing the fully functioning organelles through the systematic elimination of constituent proteins. In this study, the researchers utilize an alternative bottom-up approach and demonstrate for the first time that it is possible to construct artificial cilia-like structures from a “minimal system,” comprised of only three components. These observations suggest that emergent properties, spontaneously arising when microscopic molecular motors interact with each other, might play a role in formation of ciliary beating patterns.
Second, self-organizing processes in general have recently become the focus of considerable interest in the physics community. These processes range in scale from microscopic cellular functions and swarms of bacteria to macroscopic phenomena such as flocking of birds and manmade traffic jams. Theoretical models indicate that these vastly different phenomena can be described using similar theoretical formalisms. However, controllable experiments with flocks of birds or crowds at football stadiums are virtually impossible to conduct. The experiments described by Sanchez et al. could serve as a model system to test a broad range of theoretical predictions. Third, the reproduction of such an essential biological functionality in a simple in vitro system will be of great interest to the fields of cellular and evolutionary biology. Finally, these findings open the door for the development of one of the major goals of nanotechnology: to design motile nano-scale objects.
These encouraging results are only the first from this very new model system. The Dogic lab is currently planning refinements to the system to study these topics in greater depth.
UPDATE: Today, this publication was additionally featured on NPR Science Friday as the video pick of the week:
