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Abstract Through a variety of mechanisms, a healthy heart is able to regulate its structure and dynamics across multiple length scales. Disruption of these mechanisms can have a cascading effect, resulting in severe structural and/or functional changes that permeate across different length scales. Due to this hierarchical structure, there is interest in understanding how the components at the various scales coordinate and influence each other. However, much is unknown regarding how myofibril bundles are organized within a densely packed cell and the influence of the subcellular components on the architecture that is formed. To elucidate potential factors influencing cytoskeletal development, we proposed a computational model that integrated interactions at both the cellular and subcellular scale to predict the location of individual myofibril bundles that contributed to the formation of an energetically favorable cytoskeletal network. Our model was tested and validated using experimental metrics derived from analyzing single-cell cardiomyocytes. We demonstrated that our model-generated networks were capable of reproducing the variation observed in experimental cells at different length scales as a result of the stochasticity inherent in the different interactions between the various cellular components. Additionally, we showed that incorporating length-scale parameters resulted in physical constraints that directed cytoskeletal architecture toward a structurally consistent motif. Understanding the mechanisms guiding the formation and organization of the cytoskeleton in individual cardiomyocytes can aid tissue engineers toward developing functional cardiac tissue.
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Effects of cytoskeletal network mesh size on cargo transport
Intracellular transport of cargoes in the cell is essential for the organization and functioning cells, especially those that are large and elongated. The cytoskeletal networks inside large cells can be highly complex, and this cytoskeletal organization can have impacts on the distance and trajectories of travel. Here, we experimentally created microtubule networks with varying mesh sizes and examined the ability of kinesin-driven quantum dot cargoes to traverse the network. Using the experimental data, we deduced parameters for cargo detachment at intersections and away from intersections, allowing us to create an analytical theory for the run length as a function of mesh size. We also used these parameters to perform simulations of cargoes along paths extracted from the experimental networks. We find excellent agreement between the trends in run length, displacement, and trajectory persistence length comparing the experimental and simulated trajectories.
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- PAR ID:
- 10517106
- Publisher / Repository:
- European Physical Journal E
- Date Published:
- Journal Name:
- The European Physical Journal E
- Volume:
- 46
- Issue:
- 11
- ISSN:
- 1292-8941
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1140/epje/s10189-023-00358-8
