Biology subjects

Fiorenza, S. A.

Publications and source records attributed to Fiorenza, S. A..

5 recordsLinked to original sources

bioRxiv2026

Coordinated control of both microtubule ends regulates mitotic spindle length

The mitotic spindle is a biomechanical structure whose length must be precisely controlled to ensure faithful chromosome segregation. The treadmilling of microtubules towards centrosomes, termed poleward flux, is involved in spindle length control. However, poleward flux has been shown to be both inversely and directly proportional to spindle length, a contradiction that remains unexplained by current mechanisms. Here we introduce a model which demonstrates that length-dependent regulation at both microtubule ends allows plus- and minus-end dynamics to synchronize with one another, enabling pathways of poleward flux-based spindle length control which can rectify previous results. Moreover, our model predicts that spindle length and poleward flux can vary independently via simultaneous perturbations at both microtubule ends, which we experimentally validate with combinations of KIF18A, KIF2A, and KATNB1 depletions in human cells. Our results thus resolve a longstanding paradox and provide mechanistic insight into the reciprocal control of spindle length and poleward flux.

biophysics↗

bioRxiv2025

Distinct aneuploid karyotypes are universally selected for across cancers

Aneuploid karyotype evolution leads to immense variability in cancer patient prognosis, so characterizing relevant trends has been an important objective (1-9). Recurrent chromosome gains and losses as well as oncogenic mutations have been associated with specific cancers (10-14), but a general trend in aneuploidy evolution has not yet been identified. Here we show a universal selection principle for karyotypes composed entirely of disomies and trisomies that is conserved across many different cancer types and even in yeast. This finding is surprising enough on its own, as cancers do not typically have generalized trends, but we also see that these karyotypes exhibit a 3 times lower mutation rate of the cancer suppressor gene TP53 compared to other aneuploid karyotypes. We find that, in general, karyotypes composed of combinations of any two chromosome copy numbers, termed binary karyotypes, make up over three-quarters of the Mitelman database, which we explain by a 15% increased fitness relative to other aneuploid karyotypes. In conclusion, our results reveal binary karyotypes as a distinct category of aneuploid karyotypes that are tolerated by p53 and universally selected for independent of encoded genes or any other chromosome-specific feature, shifting the current paradigm of aneuploid cell classification.

cancer biology↗

bioRxiv2021

CyLaKS: the Cytoskeleton Lattice-based Kinetic Simulator

Interaction of cytoskeletal filaments, motor proteins, and crosslinkers drives important cellular processes including cell division and cell movement. Cytoskeletal networks also undergo nonequilibrium self-organization in reconstituted systems. An emerging problem in cytoskeletal modeling and simulation is spatiotemporal alteration of the dynamics of filaments, motors, and associated proteins. This can occur due to motor crowding and obstacles along filaments, motor interactions and direction switching, and changes, defects, and heterogeneity in the filament lattice. How such spatiotemporally varying cytoskeletal filaments and motor interactions affect their collective properties is not fully understood. We developed the Cytoskeleton Lattice-based Kinetic Simulator (CyLaKS) for problems with significant spatiotemporal variation of motor or filament properties. The simulation builds on previous work modeling motor mechanochemistry into a simulation with many interacting motors and/or associated proteins. CyLaKS also includes detailed-balance in binding kinetics and movement and lattice heterogeneity. The simulation framework is flexible and extensible for future modeling work. Here we illustrate use of CyLaKS to study long-range motor interactions, filament heterogeneity, motion of a heterodimeric motor, and how changing crosslinker number affects filament separation.

biophysics↗

bioRxiv2020

Motor guidance by long-range communication through the microtubule highway

Coupling of motor proteins within arrays drives muscle contraction, flagellar beating, chromosome segregation, and other biological processes. Current models of motor coupling invoke either direct mechanical linkage or protein crowding, which rely on short-range motor-motor interactions. In contrast, coupling mechanisms that act at longer length scales remain largely unexplored. Here we report that microtubules can physically couple motor movement in the absence of short-range interactions. The human kinesin-4 Kif4A changes the run-length and velocity of other motors on the same microtubule in the dilute binding limit, when 10-nm-sized motors are separated by microns. This effect does not depend on specific motor-motor interactions because similar changes in Kif4A motility are induced by kinesin-1 motors. A micron-scale attractive interaction potential between motors is sufficient to recreate the experimental results in a computational model. Unexpectedly, our theory suggests that long-range microtubule-mediated coupling not only affects binding kinetics but also motor mechanochemistry. Therefore, motors can sense and respond to motors bound several microns away on a microtubule. These results suggest a paradigm in which the microtubule lattice, rather than being merely a passive track, is a dynamic medium responsive to binding proteins to enable new forms of collective motor behavior.

biophysics↗

bioRxiv2019

Nanoaperture fabrication via colloidal lithography for single molecule fluorescence imaging

In single molecule fluorescence studies, background emission from labeled substrates often restricts their concentrations to non-physiological nanomolar values. One approach to address this challenge is the use of zero-mode waveguides (ZMWs), nanoscale holes in a thin metal film that physically and optically confine the observation volume allowing much higher concentrations of fluorescent substrates. Standard fabrication of ZMWs utilizes slow and costly E-beam nano-lithography. Herein, ZMWs are made using a self-assembled mask of polystyrene microspheres, enabling fabrication of thousands of ZMWs in parallel without sophisticated equipment. Polystyrene 1 m dia. microbeads self-assemble on a glass slide into a hexagonal array, forming a mask for the deposition of metallic posts in the inter-bead interstices. The width of those interstices (and subsequent posts) is adjusted within 100-300 nm by partially fusing the beads at the polystyrene glass transition temperature. The beads are dissolved in toluene, aluminum or gold cladding is deposited around the posts, and those are dissolved, leaving behind an array ZMWs. Parameter optimization and the performance of the ZMWs are presented. By using colloidal self-assembly, typical laboratories can make use of sub-wavelength ZMW technology avoiding the availability and expense of sophisticated clean-room environments and equipment.

biophysics↗