Motor processivity and speed determine structure and dynamics of microtubule-motor assemblies
- California Institute of Technology, United States
- Stanford University, United States
Abstract
Active matter systems can generate highly ordered structures, avoiding equilibrium through the consumption of energy by individual constituents. How the microscopic parameters that characterize the active agents are translated to the observed mesoscopic properties of the assembly has remained an open question. These active systems are prevalent in living matter; for example, in cells, the cytoskeleton is organized into structures such as the mitotic spindle through the coordinated activity of many motor proteins walking along microtubules. Here, we investigate how the microscopic motor-microtubule interactions affect the coherent structures formed in a reconstituted motor-microtubule system. This question is of deeper evolutionary significance as we suspect motor and microtubule type contribute to the shape and size of resulting structures. We explore key parameters experimentally and theoretically, using a variety of motors with different speeds, processivities, and directionalities. We demonstrate that aster size depends on the motor used to create the aster, and develop a model for the distribution of motors and microtubules in steady-state asters that depends on parameters related to motor speed and processivity. Further, we show that network contraction rates scale linearly with the single-motor speed in quasi one-dimensional contraction experiments. In all, this theoretical and experimental work helps elucidate how microscopic motor properties are translated to the much larger scale of collective motor-microtubule assemblies.
Data availability
All data associated with this study are stored on the CaltechData archive at DOI 10.22002/D1.2152.
Article and author information
Author details
Funding
Foundational Questions Institute (FQXi 1816)
- Rachel A Banks
- Vahe Galstyan
- Heun Jin Lee
- Soichi Hirokawa
- Matthew Thomson
- Rob Phillips
John Templeton Foundation (51250)
- Rachel A Banks
- Vahe Galstyan
- Heun Jin Lee
- Soichi Hirokawa
- Matthew Thomson
- Rob Phillips
National Institutes of Health (1R35 GM118043-01)
- Rachel A Banks
- Vahe Galstyan
- Heun Jin Lee
- Soichi Hirokawa
- Rob Phillips
John Templeton Foundation (60973)
- Rachel A Banks
- Vahe Galstyan
- Heun Jin Lee
- Soichi Hirokawa
- Matthew Thomson
- Rob Phillips
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Banks et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,297
- views
-
- 212
- downloads
-
- 7
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Motor processivity and speed determine structure and dynamics of microtubule-motor assemblies
eLife 12:e79402.
https://doi.org/10.7554/eLife.79402
Further reading
-
- Physics of Living Systems
Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a tenfold increase in stiffness (Young’s modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle and age-related factors.
-
- Cancer Biology
- Physics of Living Systems
The tumor stroma consists mainly of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions are altered during malignancy: tumor cells transform fibroblasts into cancer-associated fibroblasts, which exhibit immunosuppressive activities on which growth and metastasis depend. These include exclusion of immune cells from the tumor nest, cancer progression, and inhibition of T-cell-based immunotherapy. To understand these complex interactions, we measure the density of different cell types in the stroma using immunohistochemistry techniques on tumor samples from lung cancer patients. We incorporate these data into a minimal dynamical system, explore the variety of outcomes, and finally establish a spatio-temporal model that explains the cell distribution. We reproduce that cancer-associated fibroblasts act as a barrier to tumor expansion, but also reduce the efficiency of the immune response. Our conclusion is that the final outcome depends on the parameter values for each patient and leads to either tumor invasion, persistence, or eradication as a result of the interplay between cancer cell growth, T-cell cytotoxicity, and fibroblast activity. However, despite the existence of a wide range of scenarios, distinct trajectories, and patterns allow quantitative predictions that may help in the selection of new therapies and personalized protocols.
