Abstract
In recent years, cilia have become a research hotspot in the biomedicine field. As the important functional organelles of cells, cilia can not only perceive extracellular mechanical and chemical signals, but also transduce signals to initiate cellular responses. Based on ultrastructural and functional differences, cilia can be classified as immotile cilia or motile cilia. The immotile cilia are also called primary cilia, and its principal functions are sensing cellular antennae and transducing various morphogenetic and sensory signals. By contrast, motile cilia are usually present on a cell's surface, and the presence of dynein arms confers them with the ability to beat. Even though exteriorly the vertebrate body is bilaterally symmetric, the internal organs and associated vasculature show a clear left-right (L-R) asymmetry in the placement and patterning. L-R asymmetries in embryos occur earlier than visceral organs. Thus, for bilaterally symmetric embryo, it is a challenging problem to distinguish left from right. In the early stage of vertebrate embryonic development, there are several rotating monocilia in the embryonic node, with a 9+0 ultrastructure. Namely, the main composition of the axoneme is represented by nine surrounding doublet microtubules. The dynein in the axoneme forms bridges among neighbouring microtubule doublets, and it provides the power and control for cilia movement through ATP hydrolysis. Then, the nodal cilia rotate to drive the surrounding fluid to flow leftward, which causes the embryo to sense the left and right axis directions. Beyond that, abnormalities in the structure and function of nodal cilia can lead to serious developmental disorders. Thus, the study of nodal cilia contributes to our understanding in the developmental processes of vertebrates. The connection between cilia and L-R asymmetry originated in the mid-1970s. Through the studies of Kartagener syndrome, Afzelius and Pedersen found that the Autosomal recessive genetic disorder was caused by immotile cilia. From then on, more and more researchers have studied cilia in many aspects. Although the understanding of the structure and function of nodal cilia continues to deepen, the internal mechanism of cilia movement and the mechanism of nodal flow propagation remain questionable. This paper will summarize the progress of these studies from the molecular, cellular, and extracellular fluid levels. Above all, the related researches on cilia structure, dynein structure, and numerical simulation of dynein activity model are introduced. Furthermore, based on morphogen hypothesis, nodal vesicular parcel (NVP) hypothesis and two-cilia hypothesis, the role of nodal cilia in embryonic development and the effect of cilia position and state on pericapillary fluids are described. After that, the necessity of unidirectional nodal flow for embryo development is introduced from the aspects of transmitting small molecule signals and generating the mechanical force. At the same time, several methods for measuring flow velocity are introduced. Finally, the problems to be solved in the biomechanical research of ciliary movement are summarized and prospected. Cross-scale simulation analysis can break the inherent limitations of single-scale magnitude. In the future, research work can be carried out in the following aspects: improving experimental observation techniques, measuring the precise properties of the nodal cilia, and optimizing simulation models.
Translated title of the contribution | Advances in biomechanical studies of nodal ciliary movement |
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Original language | Chinese (Traditional) |
Pages (from-to) | 3184-3191 |
Number of pages | 8 |
Journal | Kexue Tongbao/Chinese Science Bulletin |
Volume | 63 |
Issue number | 31 |
DOIs | |
Publication status | Published - 1 Nov 2018 |