About

Meredith Betterton is a professor in the Department of Physics at the University of Colorado Boulder. Her research focuses on the physics of cell division and related biophysics, with current projects addressing motor protein dynamics and microtubule length regulation, cytoskeletal active matter, mitotic spindle assembly and regulation, chromosome segregation in cell division, and disordered proteins in the nuclear pore complex. She holds a PhD in Physics from Harvard University, earned in 2000, and a BA in Physics, magna cum laude, from Princeton University in 1994. Her honors and awards include the NIH Quantitative Research Development Award (K25) in 2014, the NSF CAREER Award in 2009, an Alfred P. Sloan Research Fellowship in 2004, and a Junior Faculty Development Award from the University of Colorado at Boulder in 2004. She also received the Chateaubriand Fellowship in 2000, the Burroughs Wellcome Fellowship in 1998, and a Harvard University Certificate of Distinction in Teaching in 1998. Her research interests are centered on understanding the physical mechanisms underlying cellular processes involved in cell division and molecular biophysics.

Research topics

• Computer Science
• Biology
• Chemistry
• Nanotechnology
• Computational chemistry
• Biological system
• Physics
• Materials science
• Cell biology
• Genetics

Selected publications

• Tracking Mitotic Spindle Dynamics and Protein Localization in Fission Yeast With <scp>FYSKA</scp> , the Fission Yeast Spindle Kymograph Analyzer

  Cytoskeleton · 2026-03-17

  articleSenior authorCorresponding

  Quantitative analysis of mitotic spindle dynamics requires accurate tracking despite challenges such as cell drift, spindle rotation, and fluctuating fluorescence signals. We developed the Fission Yeast Spindle Kymograph Analyzer (FYSKA), an automated software tool that tracks the spindle and constructs kymographs of spindle-associated proteins in Schizosaccharomyces pombe. FYSKA uses fluorescent spindle pole markers to achieve sub-pixel precision, applies error correction for transient signal loss, and maintains robustness under rotation or drift. Compared to semi-automated approaches, it generates kymographs with more consistent intensity profiles and improved capture of the spindle axis. Using FYSKA, we quantified spindle length fluctuations and examined localization patterns of the kinesin-5 motor Cut7 including asymmetric spindle pole recruitment in Cut11-7. These examples show how FYSKA enables automated, reproducible analysis of mitotic spindle organization and protein dynamics.

  PublisherDOI

• Kinesin-5/Cut7 C-terminal tail phosphorylation influence on motor regulation through multi-scale molecular modelling

  Zenodo (CERN European Organization for Nuclear Research) · 2026-05-07

  datasetOpen access

  This dataset contains essential molecular dynamics (MD) and steered molecular dynamics (SMD) simulation data for the kinesin-5/Cut7 protein, focusing on the role of C-terminal tail phosphorylation in motor regulation. The dataset includes: MD simulation data for the unphosphorylated kinesin-5 homotetramer system MD simulation data for unphosphorylated (UP) and phosphorylated (P) kinesin-5/Cut7 tail systems across three independent replicas MD simulation data for unphosphorylated (UP) and phosphorylated (P) kinesin-5/Cut7 tail–motor complexes across three independent replicas Steered MD (SMD) datasets, including force–time (pullf.xvg) and extension–time (pullx.xvg) data for all replicates from both all-atom and coarse-grained simulations To facilitate public data sharing, trajectories were processed to reduce file size while preserving the conformational dynamics relevant to the analyses presented in the associated manuscript. Specifically, processed trajectories (XTC format) were aligned to the motor domain, stripped of solvent and ions, and downsampled at 200 ps intervals. Corresponding topology/input files (TPR) and representative structure files (GRO) are included. Representative SMD trajectories and simulation parameter files (MDP) are also provided to ensure reproducibility of the simulations and analyses. Additional raw trajectories, intermediate files, and extended datasets are available from the corresponding author upon reasonable request.

  PublisherDOI

• Kinesin-5/Cut7 C-terminal tail phosphorylation influence on motor regulation through multi-scale molecular modelling

  Zenodo (CERN European Organization for Nuclear Research) · 2026-05-07

  datasetOpen access

  This dataset contains essential molecular dynamics (MD) and steered molecular dynamics (SMD) simulation data for the kinesin-5/Cut7 protein, focusing on the role of C-terminal tail phosphorylation in motor regulation. The dataset includes: MD simulation data for the unphosphorylated kinesin-5 homotetramer system MD simulation data for unphosphorylated (UP) and phosphorylated (P) kinesin-5/Cut7 tail systems across three independent replicas MD simulation data for unphosphorylated (UP) and phosphorylated (P) kinesin-5/Cut7 tail–motor complexes across three independent replicas Steered MD (SMD) datasets, including force–time (pullf.xvg) and extension–time (pullx.xvg) data for all replicates from both all-atom and coarse-grained simulations To facilitate public data sharing, trajectories were processed to reduce file size while preserving the conformational dynamics relevant to the analyses presented in the associated manuscript. Specifically, processed trajectories (XTC format) were aligned to the motor domain, stripped of solvent and ions, and downsampled at 200 ps intervals. Corresponding topology/input files (TPR) and representative structure files (GRO) are included. Representative SMD trajectories and simulation parameter files (MDP) are also provided to ensure reproducibility of the simulations and analyses. Additional raw trajectories, intermediate files, and extended datasets are available from the corresponding author upon reasonable request.

  PublisherDOI

• BPS2026 – Inference of molecular-scale mechanisms of PRC1 resistance to microtubule pair separation

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Mechanical Coupling With the Nuclear Envelope Shapes the <i>Schizosaccharomyces pombe</i> Mitotic Spindle

  Cytoskeleton · 2025-05-10 · 2 citations

  articleOpen access

  The fission yeast Schizosaccharomyces pombe divides via closed mitosis, meaning that spindle elongation and chromosome segregation transpire entirely within the closed nuclear envelope. Both the spindle and nuclear envelope must undergo shape changes and exert varying forces on each other during this process. Previous work has demonstrated that nuclear envelope expansion (Yam, He, Zhang, Chiam, & Oliferenko, 2011; Mori & Oliferenko, 2020) and spindle pole body (SPB) embedding in the nuclear envelope are required for normal S. pombe mitosis, and mechanical modeling has described potential contributions of the spindle to nuclear morphology (Fang et al., 2020; Zhu et al., 2016). However, it is not yet fully clear how and to what extent the nuclear envelope and mitotic spindle each directly shape each other during closed mitosis. Here, we investigate this relationship by observing the behaviors of spindles and nuclei in live mitotic fission yeast following laser ablation. First, we characterize these dynamics in mitotic S. pombe nuclei with increased envelope tension, finding that nuclear envelope tension can both bend the spindle and slow elongation. Next, we directly probe the mechanical connection between spindles and nuclear envelopes by ablating each structure. We demonstrate that envelope tension can be relieved by severing spindles and that spindle compression can be relieved by rupturing the envelope. We interpret our experimental data via two quantitative models that demonstrate that fission yeast spindles and nuclear envelopes are a mechanical pair that can each shape the other's morphology.

  PublisherOA PDFDOI

• PRC1 resists microtubule sliding in two distinct resistive modes due to variations in the separation between overlapping microtubules

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-02

  preprintOpen accessSenior authorCorresponding

  Crosslinked cytoskeletal filament networks provide cells with a mechanism to regulate cellular mechanics and force transmission. An example in the microtubule cytoskeleton is mitotic spindle elongation. The three-dimensional geometry of these networks, including the overlap length and lateral microtubule spacing, likely controls how forces can be regulated, but how these parameters evolve during filament sliding is unknown. Recent evidence suggests that the crosslinker PRC1 can resist microtubule sliding by two distinct modes: a braking mode and a less resistive coasting mode. To explore how molecular-scale mechanisms influence network geometry in this system, we developed a computational model of sliding microtubule pairs crosslinked by PRC1 that reproduces the experimentally observed braking and coasting modes. Surprisingly, we found that the braking mode was associated with a substantially smaller lateral separation between the crosslinked microtubules than the coasting mode. This closer separation aligns the PRC1-mediated forces against sliding, increasing the resistive PRC1 force and dramatically reducing sliding speed. The model also finds an emergent similar average sliding speed due to PRC1 resistance, because higher initial sliding speed favors the transition to braking. Together, our results highlight the importance of the three-dimensional geometric relationships between crosslinkers and microtubules.

  PublisherDOI

• Micron-scale protein transport along microtubules by kinesin-driven shepherding

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-01

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Microtubule-based long-distance transport in eukaryotic cells typically involves the binding of cargo to motors such as highly processive kinesins for unidirectional transport. An open question is whether long-distance transport can occur by mechanisms that do not require specific motor-cargo interactions and high processivity. In addition to conventional cargo such as vesicles, kinesin also shuttles non-motor microtubule-associated proteins (MAPs) to microtubule ends. Computational modeling of a system of a motor and a MAP that do not bind directly with one another unexpectedly revealed the redistribution of the MAP to microtubule plus ends, suggesting an unconventional mode of protein transport. We recapitulated this phenomenon experimentally in a minimal in vitro system using a kinesin-1 protein (K401) and PRC1, a non-motor MAP that binds diffusively on microtubules and shows no detectable binding to K401. Single-molecule imaging revealed unidirectional streams of PRC1 molecules over micron distances along microtubules. Our findings suggest that a stoichiometric excess of K401 can act as a unidirectional barrier to PRC1 diffusion. This effectively “shepherds” PRC1 to microtubule plus end without conventional motor-cargo interactions. Remarkably, we found that shepherding occurs with low kinesin processivity. Shepherding by kinesin-1 was also observed with another MAP. These findings reveal a new mechanism of transport for microtubule-bound cargo that does not require high-affinity motor-cargo binding and motor processivity, two principles conventionally invoked for cellular transport. SIGNIFICANCE STATEMENT The textbook model of intracellular transport on microtubules involves the direct binding of cargo to processive motors, which then carry the cargo over long distances. Here, we combine computational modeling and single-molecule imaging to identify an alternative mode of protein transport by which non-motor microtubule associated proteins (MAPs) can be transported over microns without direct interactions with motor proteins. We show that “protein shepherding” results from kinesin molecules biasing the diffusion of non-motor MAPs. The unconventional transport mechanism revealed here, which does not require direct motor-cargo interaction or high motor processivity, broadens our understanding of the physical mechanisms that enhance microtubule-based cargo transport in cells.

  PublisherOA PDFDOI

• PRC1 resists microtubule sliding in two distinct resistive modes due to variations in the separation between overlapping microtubules

  Molecular Biology of the Cell · 2025-07-02 · 1 citations

  articleOpen accessSenior author

  Cross-linked cytoskeletal filament networks provide cells with a mechanism to regulate cellular mechanics and force transmission. An example in the microtubule cytoskeleton is mitotic spindle elongation. The three-dimensional geometry of these networks, including the overlap length and lateral microtubule spacing, likely controls how forces can be regulated, but how these parameters evolve during filament sliding is unknown. Recent evidence suggests that the cross-linker PRC1 can resist microtubule sliding by two distinct modes: a braking mode and a less resistive coasting mode. To explore how molecular-scale mechanisms influence network geometry in this system, we developed a computational model of sliding microtubule pairs cross-linked by PRC1 that reproduces the experimentally observed braking and coasting modes. Surprisingly, we found that the braking mode was associated with a substantially smaller lateral separation between the cross-linked microtubules than the coasting mode. This closer separation aligns the PRC1-mediated forces against sliding, increasing the resistive PRC1 force and dramatically reducing sliding speed. The model also finds an emergent similar average sliding speed due to PRC1 resistance, because higher initial sliding speed favors the transition to braking. Together, our results highlight the importance of the three-dimensional geometric relationships between cross-linkers and microtubules.

  PublisherOA PDFDOI

• Author Reply to Peer Reviews of PRC1 resists microtubule sliding in two distinct resistive modes due to variations in the separation between overlapping microtubules

  2025-06-16

  peer-reviewSenior author
  PublisherDOI

• BPS2025 - Shepherding protein along a microtubule

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

Recent grants

• Mechanisms of Kinesin-5 Motors in Mitotic Spindle Assembly

  NIH · $1.3M · 2018–2023

• Collaborative Research: MODULUS: Nuclear envelope shape change coordination with chromosome segregation in mitosis in fission yeast

  NSF · $1.1M · 2022–2026

• Collaborative Research: Hydrodynamic Theories of the Dynamics, Fluctuations, Boundaries, and Shapes of Flocks

  NSF · $341k · 2011–2015

• EAGER: Biophysical Theory of Mitotic Spindle Length Instability and Self Assembly

  NSF · $115k · 2015–2017

• Assessing the Contributions of Microtubule Dynamic Instability and Microtubule Ro

  NIH · $439k · 2014–2018

Frequent coauthors

• Matthew A. Glaser

  University of Colorado Boulder

  58 shared

• Michael Shelley

  42 shared

• Adam Lamson

  32 shared

• Robert Blackwell

  Flatiron Institute

  28 shared

• Loren E. Hough

  University of Colorado Boulder

  26 shared

• Zachary R. Gergely

  University of Colorado Boulder

  22 shared

• Saad Ansari

  University of Colorado Boulder

  19 shared

• J. Richard McIntosh

  University of Colorado Boulder

  17 shared

Education

• Ph.D.

  Harvard

  2000

• B.A.

  Princeton

  1994

Awards & honors

• NIH Quantitative Research Development Award (K25), 2014
• NSF CAREER Award, 2009
• Alfred P. Sloan Research Fellowship, 2004
• Junior Faculty Development Award, Council on Research and Cr…
• Chateaubriand Fellowship, 2000