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Nat Commun
2015 Aug 17;6:7985. doi: 10.1038/ncomms8985.
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Sperm navigation along helical paths in 3D chemoattractant landscapes.
Jikeli JF
,
Alvarez L
,
Friedrich BM
,
Wilson LG
,
Pascal R
,
Colin R
,
Pichlo M
,
Rennhack A
,
Brenker C
,
Kaupp UB
.
???displayArticle.abstract??? Sperm require a sense of direction to locate the egg for fertilization. They follow gradients of chemical and physical cues provided by the egg or the oviduct. However, the principles underlying three-dimensional (3D) navigation in chemical landscapes are unknown. Here using holographic microscopy and optochemical techniques, we track sea urchin sperm navigating in 3D chemoattractant gradients. Sperm sense gradients on two timescales, which produces two different steering responses. A periodic component, resulting from the helical swimming, gradually aligns the helix towards the gradient. When incremental path corrections fail and sperm get off course, a sharp turning manoeuvre puts sperm back on track. Turning results from an ''off'' Ca(2+) response signifying a chemoattractant stimulation decrease and, thereby, a drop in cyclic GMP concentration and membrane voltage. These findings highlight the computational sophistication by which sperm sample gradients for deterministic klinotaxis. We provide a conceptual and technical framework for studying microswimmers in 3D chemical landscapes.
Figure 1. Sperm navigate along helical paths.(a) Diagram showing the averaged swimming path of unstimulated sperm (duration 1 s, see color bar). Radius r0 and pitch p0 are drawn to scale. (b) Reconstruction of the 3D swimming path far from walls. Head wiggling was used to determine the beating plane orientation. (c) The vector normal to the beating plane (blue arrows) precesses around the helical axis (h, red arrow) with fixed inclination, describing a circle on the surface of a unit sphere centred around h. Vectors are not to scale.
Figure 2. Simulated swimming paths for three prototypical flagellar waveforms.The top of each panel illustrates the swimming path, while at the bottom is shown a waveform sequence for aligned sperm head (grey) with a coloured reference point on the flagellum (left: top view; right: side view). (a) Planar and asymmetrical beating (mean flagellar curvature, K0>0) results in circular paths. (b,c) A small flagellar twist (τf>0) results in non-planar beat patterns and swimming paths. For symmetric beating (K0=0), the resulting swimming path is a twisted ribbon (b), whereas for asymmetric beating (K0>0) sperm swim on helices, and the beating plane has a constant inclination with the helix vector h (c).
Figure 3. Tracking sperm in 3D chemoattractant gradients.(a) 3D resact gradients were established by photolysis of caged resact with a Gaussian ultraviolet-beam. The calculated free resact concentration is shown as a function of space and time, accounting for continuous photo-release and diffusion. The concentration field is rotationally symmetric about an axis shown by the vertical grey line. (b) Sperm chemotaxis in a 3D resact gradient. A grey line indicates the centre of the photolyzing beam. Initially, sperm swim on a perfect helix (1). While approaching the resact field, the helix axis bends smoothly towards the gradient centre (2). When small gradual corrections of the swimming path fail and sperm get off course, a sharp directional turn is initiated (arrowheads). (c) Left: the gradient ∇c (blue) can be decomposed into components parallel ∇||c and perpendicular ∇⊥c to the helical axis (h; red). The helical axis aligns with the gradient when it rotates towards ∇⊥c. Right: the histogram (n=10 cells) shows that the direction into which the helix axis changes scatters around ∇⊥c in a deterministic rather than random manner.
Figure 4. Chemical stimulus and cellular steering responses are coupled.(a) Attractant stimulus encountered by the sperm cell moving along the trajectory shown in Fig. 3b. The stimulus (black) can be decomposed into a slowly changing stimulus baseline (sb, red) and 2 Hz oscillations superimposed onto the baseline. (b) Top view of the swimming path. The light profile of the photolyzing beam at the focal plane is shown in grey shades. The time derivative of the stimulus baseline (dsb/dt) relative to the stimulus baseline is colour coded along the path. Shortly after down the gradient swimming (red), the cell turns abruptly (‘off response'). After each ‘off response', the cell swims up the gradient again (green). (c) Relative time derivative of sb (magenta) and alignment rate (γ1; see Methods) of the helix axis with the concentration gradient (black). Phases of up the gradient and down the gradient swimming are characterized by increases (green) and decreases (red) of sb. The helix predominantly aligns with the gradient (γ1>0). However, sharp steering responses, characterized by high γ1, are observed whenever sb decreases. (d) High-frequency component of the stimulus (approximately 2 Hz oscillations). (e) The oscillatory stimulus at ca. 2 Hz (colour coded) results from the periodic component of helical swimming in the gradient. (f) Cross-correlations between the high-frequency stimulus and modulations of path curvature (κp; top) or torsion (τp; bottom) with mean values shown in black and s.d. in grey (n=10 cells). Thin red lines show the fitted model of phase-locked oscillations and its exponential amplitude decay.
Figure 5. Signalling events underlying the ‘off responses'.(a) Signalling pathway underlying chemotaxis of A. punctulata sperm. The balance of synthesis by the chemoreceptor guanylyl cyclase (GC) and hydrolysis by PDE determines intracellular cGMP concentration. cGMP levels set the membrane potential of the cell via a cyclic nucleotide-gated K+-selective channel (CNGK). When sperm hyperpolarize, intracellular alkalization via a Na+/H+ exchanger (sNHE) and depolarization via hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels prime the sperm-specific Ca2+ channel (CatSper) to open. When cGMP synthesis ceases, the cell quickly depolarizes, more CatSper channels open and a strong steering ‘off response' takes place. (b) Relative changes in [Ca2+]i (ΔF/F0; top) and relative changes in membrane potential Vm detected with a ratiometric dye (ΔR; bottom) of sperm suspensions on release cGMP by light pulses of 180, 500 or 1,000 ms duration. Release of cGMP results in a rapid hyperpolarization and depolarization of sperm followed by a rise in [Ca2+]i (‘on response'). When photolysis ceases, a second Ca2+ signal takes place (‘off response').
Figure 6. Theoretical model for sperm steering.(a,b) Path curvature (κp; a) and torsion (τp; b) predicted by theory as a function of the mean flagellar curvature K0 and flagellar twist τf. The range of experimentally measured values is shown as contour lines (solid: mean, dashed: mean±s.d.). Labelled circles correspond to the beat patterns used in Fig. 2a–c. Only one pair (K0=0.035 μm−1, τf=4.8 × 10−3 μm−1) produces a helical path with the observed mean path curvature and path torsion (encircled c). (c) Computed swimming path (left) resulting from modulating K0 at the frequency of helical swimming. The colour coding and the graph to the right show K0. Smooth bending of the helical path accounts for gradual ‘on responses'. The helical centre line is shown in red. (d) A pulse-like change of K0 accounts for sharp helix turns during ‘off responses'. (e) Computed path of a cell navigating in a chemoattractant gradient (grey shades), where K0 is dynamically adjusted by a simple steering feedback (combining a response to fast stimulus oscillations and a dynamic regulation of feedback strength by slow changes of the stimulus baseline, see Supplementary Note 1). (f) Relative change in baseline stimulus and alignment rate (γ1) for the simulated path shown in e.
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