Unraveling the Kinematics of Sperm Motion by Reconstructing the Flagellar Wave Motion in 3D

Abstract

The flagellar wave originates from the 9+2 axoneme structure at the central core of the flagellum, where nine pairs of outer microtubule doublets are mechanically linked to a central pair. [2] The sequential sliding of the nine outer microtubules via dynein arms over the neighboring doublet bends the flagellum in 3D to produce a flagellar waveform. [3] This beating behavior is self-regulatory in nature, triggered by the combined activity of dynein motors. [3a,4] Several regulation mechanisms have been suggested to control the flagellar waveform in space and time including the local curvature-controlled dynein motor activity, [4,5] selective activation/deactivation of sliding microtubules due to transverse forces, [6] and regulation of dynein motor activity because of the sliding forces. [7] The resulting motion is 3D in nature, with the flagellar wave starting from the midpiece and traveling along a conical helix toward the end of the flagellum, causing the whole sperm body to counter-rotate. [8] Consequently, the flagellar waveform and sperm swimming path display helical, [5a,8a,c,9] twisted-planar, [8e] Sperm swim through the female reproductive tract by propagating a 3D flagellar wave that is self-regulatory in nature and driven by dynein motors. Traditional microscopy methods fail to capture the full dynamics of sperm flagellar activity as they only image and analyze sperm motility in 2D. Here, an automated platform to analyze sperm swimming behavior in 3D by using thinlens approximation and high-speed dark field microscopy to reconstruct the flagellar waveform in 3D is presented. It is found that head-tethered mouse sperm exhibit a rolling beating behavior in 3D with the beating frequency of 6.2 Hz using spectral analysis. The flagellar waveform bends in 3D, particularly in the distal regions, but is only weakly nonplanar and ambidextrous in nature, with the local helicity along the flagellum fluctuating between clockwise and counterclockwise handedness. These findings suggest a nonpersistent flagellar helicity. This method provides new opportunities for the accurate measurement of the full motion of eukaryotic flagella and cilia which is essential for a biophysical understanding of their activation by dynein motors.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smtd.202101089.

A chemomechanical model of sperm locomotion reveals two modes of swimming

“…Incorporating more detailed morphological and mechanical features may be essential to capture certain characteristics of sperm locomotion [44] and may also help shed light on variations in sperm performance [45]. Our current model is also limited to planar deformations, while recent experimental evidence suggests that flagellar deformations may in fact be three-dimensional [46,47]: accounting for 3D deformations would require a more detailed description of the axonemal structure and of the elastodynamics of the flagellum, for instance as an active Kirkhoff rod [27]. Other improvements to the present work could include a model for internal dissipation inside the flagellum, which may be significant as suggested by recent observations [48], as well as for the coupling of dynein activity with calcium signaling [23,25,49].…”

The human sperm head spins with a conserved direction during swimming in 3D

“…Human sperm spinning has been observed to be mono-directed (Linnet, 1979;Smith et al, 2009b;Phillips, 1983;Woolley, 1977), bidirected (Ishijima et al, 1992;Dardikman-Yoffe et al, 2020;Drake, 1974), and even intermittently directed (Bukatin et al, 2015). However, such reported variety in spinning direction appears to contradict observations of a conserved helical beating of human sperm flagellum (Bukatin et al, 2015;Ishijima et al, 1992;Linnet, 1979;Powar et al, 2022;Zhao et al, 2022), and conserved chirality of structural components in mammalian sperm flagella (Fawcett, 1975;Leung et al, 2021), with no agreement as to the direction of rotation reported in earlier studies (Woolley, 1977;Bishop, 1958;Drake, 1974;Yeung and Woolley, 1984;Woolley, 1979;Blokhuis, 1961;Daloglu et al, 2018).…”

Elastohydrodynamic mechanisms govern beat pattern transitions in eukaryotic flagella

“…The analysis above suggests that it is possible to exploit measurements of viscosities at which 2D-3D transitions in beat patterns to extract quantitative estimates of internal forcing. Recently, a microfluidic device was used to systematically study the effect of varying viscosity on the flagellar waveforms of single sperm cells 57 . Transitional viscosities obtained in such devices could be combined with independent measurements of the bending stiffness and compared with results from detailed simulations that account for features that have been neglected here (e.g.…”