Biology subjects

Zaferani, M.

Publications and source records attributed to Zaferani, M..

5 recordsLinked to original sources

bioRxiv2026

Emergence of large-scale polar microtubule swarms for dense molecular transport

Microtubules (MTs) and their motor proteins collectively harness chemical energy to generate mechanical work, driving some of the most coordinated self-organized dynamics in living cells. The unique properties of these molecules also make them versatile building blocks of cytoskeletal active matter and biomimetic nanomachines that recapitulate cellular motility, emergent pattern formation, and motor-driven transport. However, these canonical systems use MTs of fixed length and do not incorporate the natural ability of MTs to grow and regenerate. Here, we go beyond these limits by using dynamic self-amplifying branched MT networks. Driven by kinesin-1 and cytoplasmic dynein activity, surface-gliding branched MT bundles undergo swarming that yields large-scale collective MT architectures with several sought-after features. They are polar and orientationally aligned, dense, span millimeter scales, and persist over hours. We then show that these features enable molecular transport along the swarm at unprecedented capacities, with up to six million motor complexes walking in parallel across millimeter-scale distances over hours. Our results introduce a new regime in cytoskeletal active matter in which the interplay between motor-driven activity and filament generation via branching leads to emergent polar order in proliferating swarms. Such emergent polarity makes these swarms suitable for engineering scalable transport nanotechnologies and programmable soft materials.

biophysics↗

bioRxiv2025

Sperm hyperactivation drives a circling-and-wandering migration strategy

During migration through the female reproductive tract, sperm undergo physiological changes known as capacitation, including a motility transition termed hyperactivation. Hyperactivation is essential for various aspects of fertilization, particularly effective migration within the tract. However, how hyperactivation facilitates this migration remains elusive. Here, we profiled bull sperm hyperactivation in Newtonian and complex fluids near microfluidic surfaces, mimicking generic swimming conditions in the tract. We identified three swim gaits: wandering (persistent random walks), circling, and an intriguing circling-and- wandering mode marked by stochastic transitions between the two. All gaits exhibit diffusive behavior over long time scales, with wandering showing a tenfold higher diffusivity than circling, and the diffusivity of circling-and-wandering falling in between. We found that while wandering sperm scatter from convex and concave surfaces, circling sperm become trapped around pillars, highlighting the distinctive nature of each phase. Additionally, stochastic simulations of swimming in porous media showed that as the geometrical complexity of the environment increases, circling-and-wandering outperforms either strategy alone in spreading through the media. Our findings suggest that while wandering promotes exploration and circling supports local exploitation, circling-and-wandering combines the strengths of both strategies by balancing exploration and exploitation to adapt motility, enhance migration, and potentially improve target search.

biophysics↗

bioRxiv2024

Boundary-Sensing Mechanism in Branched Microtubule Networks

The self-organization of cytoskeletal networks in confined geometries requires sensing and responding to mechanical cues at nanometer to micron scales that allow for dynamic adaptation. Here, we show that the branching of microtubules (MTs) via branching MT nucleation combined with dynamic instability constitutes a boundary-sensing mechanism within confined spaces. Using a nanotechnology platform, we observe the self-organization of a branched MT network in a channel featuring a narrow junction and a closed end. Our observations reveal that branching MT nucleation occurs in the post-narrowing region only if that region exceeds a certain length before it terminates at the channels closed end. The length-dependent occurrence of branching MT nucleation arises from the dynamic instability of existing MTs when they interact with the channels closed end, combined with the specific timescale required for new MTs to nucleate at a point distant from the closed end, creating a mechanical feedback. Increasing the concentration of the base branching factor TPX2 accelerates nucleation kinetics and thus tunes the minimum length scale needed for occurrence of branching MT nucleation. As such, this feedback not only allows for adaptation to the local geometry, but also allows for tunable formation of MT networks in narrow (micron and submicron scale) channels. However, while a high concentration of TPX2 increases the kinetic rate of branching MT nucleation, it also stabilizes MTs at the channels closed end leading to MT growth and nucleation in the reversed direction, and thus hinders boundary sensing. After experimental characterization of boundary-sensing feedback, we propose a minimal model and execute numerical simulations. We investigate how this feedback, wherein growing MTs dynamically sense their physical environment and provide nucleation sites for new MTs, sets a length/time scale that steers the architecture of MT networks in confined spaces. This "search- and-branch" mechanism has implications for the formation of MT networks during neuronal morphogenesis, including axonal growth and the formation of highly branched dendritic networks, as well as for plant development and MT-driven guidance in fungi, and engineering nanotechnologies.

bioengineering↗

bioRxiv2023

Building on-chip cytoskeletal circuits via branched microtubule networks

Controllable platforms to engineer robust cytoskeletal scaffolds have the potential to create novel on-chip nanotechnologies. Inspired by axons, we combined the branching microtubule (MT) nucleation pathway with microfabrication to develop "cytoskeletal circuits". This active matter platform allows control over the adaptive self-organization of uniformly polarized MT arrays via geometric features of microstructures designed within a microfluidic confinement. We build and characterize basic elements, including turns and divisions, as well as complex regulatory elements, such as biased division and MT diodes, to construct various MT architectures on a chip. Our platform could be used in diverse applications, ranging from efficient on-chip molecular transport to mechanical nano-actuators. Further, cytoskeletal circuits can serve as a tool to study how the physical environment contributes to MT architecture in living cells. SignificanceMicrotubules have essential functions within the cell, including providing a robust railroad for motor-driven cargo transport. The unique properties of microtubules have stimulated attempts to harness these characteristics for targeted delivery of molecular complexes, novel material design, and developing nanotechnologies with precision comparable to living organisms. However, Previous efforts mainly focused on microtubules with fixed length and layout and no controlled MT generation, setting a limit on designing MT architecture. In this study, we integrated nanofabrication with microtubule branching reactions borrowed directly from the cells toolkit to construct cytoskeletal circuits and generate microtubule architectures from scratch. That is, our system enables control over microtubule growth and autocatalytic nucleation on a microfluidic chip with micro/nanostructures patterned within.

bioengineering↗

bioRxiv2020

Effect of flagellar beating pattern on sperm rheotaxis and boundary-dependent navigation

The study of navigational mechanisms used by mammalian sperm inside a microenvironment yields better understanding of sperm locomotion during the insemination process, which aids in the design of tools for overcoming infertility. Near- and far-field hydrodynamic interactions with nearby boundaries and rheotaxis are known to be some of the steering strategies that keep sperm on the correct path toward the egg. However, it is not known how the beating patterns of sperm may influence these navigational strategies. In this study, we investigate the effect of flagellar beating pattern on navigation of sperm cells both theoretically and experimentally using a two-step approach. We first isolate bovine sperm based on their rheotactic behavior in a zone with quiescent medium using a microfluidic system. This step ensures that the swimmers are able to navigate upstream and have motilities higher than a selected value, even though they feature various flagellar beating patterns. We then explore the flagellar beating pattern of these isolated sperm and their subsequent influence on boundary-dependent navigation. Our findings indicate that rheotaxis enables sperm to navigate upstream even in the presence of circular motion in their motility, whereas boundary-dependent navigation is more sensitive to the circular motion and selects for progressive motility. This finding may explain the clinical importance of progressive motility in semen samples for fertility, as the flow of mucus may not be sufficiently strong to orient the sperm cells throughout the process of insemination. SignificanceFinding the egg and moving toward it while traversing the complex structure of the female reproductive tract is necessary for mammalian sperm. Previous studies have shown how sperm use navigational steering mechanisms that are based on swimming upstream (i.e. rheotaxis) and along the boundaries of the female reproductive tract. We demonstrate that the performance of theses navigational mechanisms is associated with the primary characteristics of sperm motility. In fact, sperm rheotaxis is more sensitive to the motility and thus average velocity of sperm while navigation via rigid boundaries is more sensitive to the flagellar beating pattern and selects for symmetric beating. Our results can be expanded to other autonomous microswimmers and their subsequent navigation mechanisms.

biophysics↗