Emergent Microtubule Networks For High-Throughput Molecular Transport (In Prep)
Sperm Chemotaxis: Circling-and-Wandering
As sperm migrate through the female reproductive tract, they undergo a transition called hyperactivation—a shift in swimming behavior essential for fertilization. We studied bull sperm in simple and complex fluids near microfluidic surfaces and discovered three distinct motility modes: wandering, circling, and a mixed circling-and-wandering mode involving spontaneous and stochastic switching between the two. While wandering enables wide exploration and circling promotes local trapping, the mixed mode balances both, enhancing navigation in complex environments. Simulations in porous media revealed that this hybrid behavior improves spreading in complex enviroment, and suggesting an adaptive chemotactic strategy for efficient migration and target search.
Under Revision in Nature Communications, BioRxiv (2025)
Boundary-Sensing Mechanism
In living cells, the organization of microtubules depends on their ability to sense and adapt to confined environments like cellular protrusions. This research explores how microtubules self-organize under such constraints by studying branched microtubule networks inside extremely narrow microstructures that mimic the tight spaces found in cells. We discovered a form of "boundary sensing," where microtubule growth and branching occur only beyond a critical distance from a closed end—determined by microtubule dynamics and the timing of nucleation events.
By combining experiments and simulations, we further investigated this process and showed how a tunable feedback system adaptively shapes microtubule architecture, as pioneering microtubules navigate their confined surroundings and generate new nucleation sites.
These findings provide insight into how microtubules guide growth in neurons, fungi, and plants, and suggest new strategies for engineering active materials and technologies.
Cytoskeletal Circuits
Cytoskeletal elements self-organize into intricate hierarchical structures, forming the molecular basis for various cellular functions. A remarkable example is the axonal microtubule architecture, crucial for controlled neuronal migration, axon extension, and long-distance molecular transport. To harness this natural phenomenon, we have developed cytoskeletal circuits as controllable platforms to engineer robust microtubule architectures. These circuits integrate the branching microtubule nucleation pathway with microfabrication techniques, enabling the adaptive self-organization of uniformly polarized microtubule arrays within microfluidic confinements. Our microfluidic structures provide control over this self-organizing process (first video on the right), allowing us to construct diverse microtubule architectures on a chip. Examples include simple components such as straight channels and symmetric and asymmetric divisions (second video on the right), as well as complicated regulatory elements such as biased division and microtubuel diode.
Our work holds potential for the development of novel on-chip nanotechnologies.
Sperm Biphasic Chemokinesis
In this study, we discovered that in response to biochemical clues, sperm exhibit two types of motion, chiral (swimming in circles) and hyperactive (random reorientation), depending on the rheological properties of the media. By analyzing these trajectories and using theoretical modeling, we found that the diffusivity of these motions decreases with higher concentrations of chemical stimulants. This concentration-dependent chemokinesis suggests that sperm refine their search area within different functional regions of the female reproductive tract. Additionally, sperm's ability to switch between these motion phases indicates the use of stochastic navigational strategies in the dynamic and diverse FRT environment.
Sperm Navigation along Physical Boundaries
Sperm navigating within the female reproductive tract face challenges, but hyperactivation in the oviduct helps them adapt for successful fertilization. By studying bovine sperm in microfluidic reservoirs and using modeling, we discovered that hyperactivation influences sperm's interactions with physical boundaries, affecting their navigation. Sperm initially swim along the reservoir sidewalls, but hyperactivation changes their behavior. Noise near a critical curvature value leads to a "Run-Stop" motion. Hyperactivation also creates a pseudo-chemotaxis effect, with sperm remaining longer in chambers with higher agonist concentrations.
Sperm Selection
Using a microfluidic device featuring a stricture that simulates the fluid mechanical properties of narrow junctions inside the female reproductive tract, we documented the gate-like role played by the stricture in preventing sperm with motilities below a certain threshold from advancing through the stricture to the other side (i.e., fertilization site). All the slower sperm accumulate below (i.e., in front of) the stricture and swim in a butterfly-shaped path between the channel walls, thus maintaining the potential for penetrating the stricture and ultimately advancing toward the fertilization site. Accumulation below the stricture occurs in a hierarchical manner so that dense concentrations of sperm with higher velocities remain closer to the stricture, with more sparsely distributed arrays of lower-velocity sperm lagging behind.