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1. Quantification of microtubule stutters: dynamic instability behaviors that are strongly associated with catastrophe

   https://doi.org/10.1091/mbc.E20-06-0348  

   Mahserejian, Shant M.; Scripture, Jared P.; Mauro, Ava J.; Lawrence, Elizabeth J.; Jonasson, Erin M.; Murray, Kristopher S.; Li, Jun; Gardner, Melissa; Alber, Mark; Zanic, Marija; et al (March 2022, Molecular Biology of the Cell)

   Walczak, Claire (Ed.)

   Microtubules (MTs) are cytoskeletal fibers that undergo dynamic instability (DI), a remarkable process involving phases of growth and shortening separated by stochastic transitions called catastrophe and rescue. Dissecting DI mechanism(s) requires first characterizing and quantifying these dynamics, a subjective process that often ignores complexity in MT behavior. We present a Statistical Tool for Automated Dynamic Instability Analysis (STADIA) that identifies and quantifies not only growth and shortening, but also a category of intermediate behaviors that we term “stutters.” During stutters, the rate of MT length change tends to be smaller in magnitude than during typical growth or shortening phases. Quantifying stutters and other behaviors with STADIA demonstrates that stutters precede most catastrophes in our in vitro experiments and dimer-scale MT simulations, suggesting that stutters are mechanistically involved in catastrophes. Related to this idea, we show that the anticatastrophe factor CLASP2γ works by promoting the return of stuttering MTs to growth. STADIA enables more comprehensive and data-driven analysis of MT dynamics compared with previous methods. The treatment of stutters as distinct and quantifiable DI behaviors provides new opportunities for analyzing mechanisms of MT dynamics and their regulation by binding proteins. 

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2. Relationship between dynamic instability of individual microtubules and flux of subunits into and out of polymer

   https://doi.org/10.1002/cm.21557  

   Mauro, Ava J.; Jonasson, Erin M.; Goodson, Holly V. (September 2019, Cytoskeleton)

   Abstract Behaviors of dynamic polymers such as microtubules and actin are frequently assessed at one or both of the following scales: (a) net assembly or disassembly of bulk polymer, (b) growth and shortening of individual filaments. Previous work has derived various forms of an equation to relate the rate of change in bulk polymer mass (i.e., flux of subunits into and out of polymer, often abbreviated as “J”) to individual filament behaviors. However, these versions of the “Jequation” differ in the variables used to quantify individual filament behavior, which correspond to different experimental approaches. For example, some variants of theJequation use dynamic instability parameters, obtained by following particular individual filaments for long periods of time. Another form of the equation uses measurements from many individuals followed over short time steps. We use a combination of derivations and computer simulations that mimic experiments to (a) relate the various forms of theJequation to each other, (b) determine conditions under which theseJequation forms are and are not equivalent, and (c) identify aspects of the measurements that can affect the accuracy of each form of theJequation. Improved understanding of theJequation and its connections to experimentally measurable quantities will contribute to efforts to build a multiscale understanding of steady‐state polymer behavior. 

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3. The force response of muscles to activation and length perturbations depends on length history

   https://doi.org/10.1242/jeb.243991  

   Jeong, Siwoo; Nishikawa, Kiisa (February 2023, Journal of Experimental Biology)

   ABSTRACT Recent studies have demonstrated that muscle force is not determined solely by activation under dynamic conditions, and that length history has an important role in determining dynamic muscle force. Yet, the mechanisms for how muscle force is produced under dynamic conditions remain unclear. To explore this, we investigated the effects of muscle stiffness, activation and length perturbations on muscle force. First, submaximal isometric contraction was established for whole soleus muscles. Next, the muscles were actively shortened at three velocities. During active shortening, we measured muscle stiffness at optimal muscle length (L0) and the force response to time-varying activation and length perturbations. We found that muscle stiffness increased with activation but decreased as shortening velocity increased. The slope of the relationship between maximum force and activation amplitude differed significantly among shortening velocities. Also, the intercept and slope of the relationship between length perturbation amplitude and maximum force decreased with shortening velocity. As shortening velocities were related to muscle stiffness, the results suggest that length history determines muscle stiffness and the history-dependent muscle stiffness influences the contribution of activation and length perturbations to muscle force. A two-parameter viscoelastic model including a linear spring and a linear damper in parallel with measured stiffness predicted history-dependent muscle force with high accuracy. The results and simulations support the hypothesis that muscle force under dynamic conditions can be accurately predicted as the force response of a history-dependent viscoelastic material to length perturbations. 

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4. Multiscale Spatial Patterns in Giant Dike Swarms Identified Through Objective Feature Extraction

   https://doi.org/10.1029/2022GC010842  

   Kubo_Hutchison, A; Karlstrom, L; Mittal, T (September 2023, Geochemistry, Geophysics, Geosystems)

   Dike swarms are ubiquitous on terrestrial planets and represent the frozen remnants of magma transport networks. However, spatial complexity, protracted emplacement history, and uneven surface exposure typically make it difficult to quantify patterns in dike swarms on different scales. In this study, we address this challenge using the Hough transform (HT) to objectively link dissected dike segments and analyze multiscale spatial structure in dike swarms. We apply this method to swarms of three scales: the Spanish Peaks, USA; the Columbia River Flood Basalt Group (CRBG), USA; the Deccan Traps Flood Basalts, India. First, we cluster dike segments in HT space, recognizing prevalent linearly aligned structures that represent single dikes or dike packets, with lengths up to 10 −  30x the mapped mean segment length. Second, we identify colinear and radial dike segment mesoscale structures within each data set, using the HT to segment swarms into constituent spatial patterns. We show that for both the CRBG and Deccan Traps, a single radial or circumferential swarm does not well characterize the data. Instead, multiple and sometimes overlapping mesoscale linear and radial features are prevalent suggesting a complex history of crustal stresses. The HT can provide useful insights in a variety of geologic settings where many quasi‐linear features, at any scale, are superimposed spatially. 

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5. Behaviors of individual microtubules and microtubule populations relative to critical concentrations: dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis

   https://doi.org/10.1091/mbc.E19-02-0101  

   Jonasson, Erin M.; Mauro, Ava J.; Li, Chunlei; Labuz, Ellen C.; Mahserejian, Shant M.; Scripture, Jared P.; Gregoretti, Ivan V.; Alber, Mark; Goodson, Holly V.; Mogilner, Alex (March 2020, Molecular Biology of the Cell)

   The concept of critical concentration (CC) is central to understanding the behavior of microtubules (MTs) and other cytoskeletal polymers. Traditionally, these polymers are understood to have one CC, measured in multiple ways and assumed to be the subunit concentration necessary for polymer assembly. However, this framework does not incorporate dynamic instability (DI), and there is work indicating that MTs have two CCs. We use our previously established simulations to confirm that MTs have (at least) two experimentally relevant CCs and to clarify the behavior of individuals and populations relative to the CCs. At free subunit concentrations above the lower CC (CC Elongation ), growth phases of individual filaments can occur transiently; above the higher CC (CC NetAssembly ), the population’s polymer mass will increase persistently. Our results demonstrate that most experimental CC measurements correspond to CC NetAssembly , meaning that “typical” DI occurs below the concentration traditionally considered necessary for polymer assembly. We report that [free tubulin] at steady state does not equal CC NetAssembly , but instead approaches CC NetAssembly asymptotically as [total tubulin] increases, and depends on the number of stable MT nucleation sites. We show that the degree of separation between CC Elongation and CC NetAssembly depends on the rate of nucleotide hydrolysis. This clarified framework helps explain and unify many experimental observations. 

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