Helical vasculogenesis driven by cell chirality

Authors
Zhang, Haokang
ORCID
https://orcid.org/0000-0002-4313-4768
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Other Contributors
Hahn, Mariah, S
Thompson, Deanna, M
Adam, Alejandro, P
Wan, Leo, Q
Issue Date
2023-12
Keywords
Biomedical engineering
Degree
PhD
Terms of Use
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute (RPI), Troy, NY. Copyright of original work retained by author.
Full Citation
Abstract
The morphogenesis of tubular structures is well-known for its crucial roles in development and disease, such as the formation of the cardiovascular system, which is among the first to exhibit left-right (LR) asymmetry. Nevertheless, the underlying mechanism governing this intricate phenomenon remains largely unexplored, leaving a significant knowledge gap, particularly in the context of recreating it in the well-controlled engineering systems. Leveraging advanced microfluidics and image processing, we present compelling evidence of the spontaneous emergence of helical endothelial tubes exhibiting a robust right-handedness governed by the inherent cell chirality, independent of vascular flow profile and substrate stiffness. To strengthen our findings, we also identify a consistent bias towards the same chirality in mouse retinal and aortic vascular tissues. Intriguingly, manipulating the chirality of endothelial cells through the administration of small-molecule drugs produces a dose-dependent reversal of the handedness in the engineered vessels, accompanied by non-monotonic changes in vascular permeability. Moreover, by probing into the biomechanical factors associated with this phenomenon, we demonstrate that the substrate surface curvatures and tissue fluidity play important roles in its regulation. In summary, our study unravels a novel mechanism underlying vascular chiral morphogenesis, shedding light on the broader implications and distinctive perspectives of tubulogenesis within biological systems.
Description
December2023
Department
Publisher
Rensselaer Polytechnic Institute, Troy, NY
Relationships
Rensselaer Theses and Dissertations Online Collection
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