Human spermatozoa migration in microchannels reveals boundary-following navigation

Abstract

The migratory abilities of motile human spermatozoa in vivo are essential for natural fertility, but it remains a mystery what properties distinguish the tens of cells which find an egg from the millions of cells ejaculated. To reach the site of fertilization, sperm must traverse narrow and convoluted channels, filled with viscous fluids. To elucidate individual and group behaviors that may occur in the complex three-dimensional female tract environment, we examine the behavior of migrating sperm in assorted microchannel geometries. Cells rarely swim in the central part of the channel cross-section, instead traveling along the intersection of the channel walls ("channel corners"). When the channel turns sharply, cells leave the corner, continuing ahead until hitting the opposite wall of the channel, with a distribution of departure angles, the latter being modulated by fluid viscosity. If the channel bend is smooth, cells depart from the inner wall when the curvature radius is less than a threshold value close to 150 μm. Specific wall shapes are able to preferentially direct motile cells. As a consequence of swimming along the corners, the domain occupied by cells becomes essentially one-dimensional, leading to frequent collisions, and needs to be accounted for when modeling the behavior of populations of migratory cells and considering how sperm populate and navigate the female tract. The combined effect of viscosity and three-dimensional architecture should be accounted for in future in vitro studies of sperm chemoattraction.

Fig. 1.

Schematic of inferred cell migratory behavior. Cells swim head against the wall, ending up swimming along corners; on sharp turns, cells depart from channel walls (A). Qualitative explanation of why the cells swim head against the wall (B) and an estimate of the cell minimum turning radius (C).

Fig. 2.

A typical superposition of an image sequence; top view of the microchannel. Cell positions in successive frames are color-coded as red-green-blue to resolve the swimming direction. The space between microchannels is shaded gray to indicate position of walls. Edges of gray shading are spaced from channel walls by approximately 15 μm so that they do not interfere with tracks of the cells. Most of cells swim along the intersection of the channel vertical and horizontal walls (A) with few tracks observed in the middle of the channel. At the periphery of the image where the “side” wall of the channel is observed at an angle, cells traveling along in top and bottom corners between channel walls can be distinguished (B). When the channel turns, cells depart from the wall (C). As a result, no cells travel along the inner corners after the turn (D). In a curved channel, some cells continue to travel along the wall and some depart (E). Cells may also depart from the wall on collision with each other (F) which is shown in Fig. 3 with a greater magnification.

Fig. 3.

Cells may depart from walls on collision. The image on the left is composed of nine consequent frames and shows a head-on collision; here, the beginning of the track of the departed cell is overdrawn by the track of the cell that stayed attached and is not visible. The image on the right is composed of 17 consequent frames and shows a collision when one sperm cell overtakes another. The time interval between images is one-quarter of a second. Cell swimming directions are indicated with dotted arrows; positions of the cells in first and last images of sequences are indicated by solid arrows. Location of the channel walls are indicated by gray shading.

Fig. 4.

Spermatozoa in the “one way running track” microchannel geometry. The space outside the microchannel is shaded gray to indicate position of the walls. Edges of gray shading are spaced from channel walls by approximately 10–20 μm so that they do not interfere with tracks of the cells. The long arrow shows the preferred (counterclockwise) direction of cell migration. The arrow in the zoomed insert of the channel segment points at a track of a cell swimming in the direction opposite to that dictated by features of channel walls. Follow the track to see this cell departing from the inside of the ratchet and traversing the channel, being redirected counterclockwise, as the other cells travel.

Fig. 5.

Distribution of the angle of cell departure from the inner wall on a 90° bend of the channel. Zero angle corresponds to the cell continuing motion without turning; positive angles correspond to cells turning in the same direction as the channel bends.