Biophysics, Reproductive biomechanics, Microswimmers, Microfluidics
My research is to identify the navigational mechanisms associated with mammalian sperm migration within the complex and dynamic environment of the female reproductive tract. On the experimental side, we design and fabricate microfluidic structures to explore sperm motion within confined spaces and identify the biophysical and biochemical clues that promote navigational mechanisms. On the theoretical side, we employ approaches from fluid mechanics, nonlinear dynamics, and statistical physics to develop quantitative models that describe these navigational mechanisms.
In the early stages of this research, we focused on two navigational mechanisms: sperm upstream swimming (rheotaxis) and the boundary-following navigation caused by hydrodynamic interactions of sperm with nearby rigid boundaries. We discovered that sperm rheotaxis and boundary-following navigation are the basis for an emergent fierce competition among sperm, during which the female reproductive tract selects for the most vigorous ones (Zaferani et al. 2018, PNAS; Zaferani et al., 2019, Sci Adv).
In the next stage, we became interested in mammalian sperm rolling along its longitudinal axis. This long-observed component of motility is specific to mammalian sperm and its function in the fertilization process has remained unknown for decades. We discovered that sperm rolling is sensitive to ambient fluid viscosity and viscoelasticity. That is, at low ambient viscosity and viscoelasticity, the frequent form of rolling promotes efficient rheotaxis and boundary-following navigation. Whereas high ambient viscosities or viscoelasticities suppress rolling; consequently, sperm exhibit a diffusive circular motion with inefficient rheotactic and boundary-following motion. Because the viscosity and viscoelasticity of the fluid within the female tract varies according to functional region, the tract can regulate sperm navigation via controlling the rolling component. Unlike sperm of marine invertebrates, there is no strong evidence for a deterministic chemotactic behavior in mammalian sperm. However, it is known that in response to certain chemical stimuli, mammalian sperm motility transforms, and becomes “hyperactivated”. This hyperactivated motility is concentration-dependent and reversible but does not result in a deterministic chemotaxis. Accordingly, the role of chemical stimuli in mammalian sperm navigation is a mystery. Focusing on sperm hyperactivation, we discovered that the hyperactivation level controls sperm motion within microenvironments at high and low ambient viscosities and viscoelasticities, which subsequently stimulates a previously unknown pseudo-chemotaxis.