Embryonic morphogenesis is a biological process which depicts shape forming of tissues and organs during development. Unveiling the roles of mechanical forces generated, transmitted, and regulated in cells and tissues through these processes is key to understanding the biophysical mechanisms governing morphogenesis. To this end, it is imperative to measure, simulate, and predict the regulation and control of these mechanical forces during morphogenesis. This article aims to provide a comprehensive review of the recent advances on mechanical properties of cells and tissues, generation of mechanical forces in cells and tissues, the transmission processes of these generated forces during cells and tissues, the tools and methods used to measure and predict these mechanical forces in vivo, in vitro, or in silico, and to better understand the corresponding regulation and control of generated forces. Understanding the biomechanics and mechanobiology of morphogenesis will not only shed light on the fundamental physical mechanisms underlying these concerted biological processes during normal development, but also uncover new information that will benefit biomedical research in preventing and treating congenital defects or tissue engineering and regeneration.
Dynamic mechanobiology of cardiac cells and tissues: Current status and future perspective
Mechanical forces impact cardiac cells and tissues over their entire lifespan, from development to growth and eventually to pathophysiology. However, the mechanobiological pathways that drive cell and tissue responses to mechanical forces are only now beginning to be understood, due in part to the challenges in replicating the evolving dynamic microenvironments of cardiac cells and tissues in a laboratory setting. Although many in vitro cardiac models have been established to provide specific stiffness, topography, or viscoelasticity to cardiac cells and tissues via biomaterial scaffolds or external stimuli, technologies for presenting time-evolving mechanical microenvironments have only recently been developed. In this review, we summarize the range of in vitro platforms that have been used for cardiac mechanobiological studies. We provide a comprehensive review on phenotypic and molecular changes of cardiomyocytes in response to these environments, with a focus on how dynamic mechanical cues are transduced and deciphered. We conclude with our vision of how these findings will help to define the baseline of heart pathology and of how these in vitro systems will potentially serve to improve the development of therapies for heart diseases.
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- PAR ID:
- 10438608
- Date Published:
- Journal Name:
- Biophysics Reviews
- Volume:
- 4
- Issue:
- 1
- ISSN:
- 2688-4089
- Page Range / eLocation ID:
- 011314
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
Studies in animal models tracing organogenesis of the mesoderm-derived heart have emphasized the importance of signals coming from adjacent endodermal tissues in coordinating proper cardiac morphogenesis. Although in vitro models such as cardiac organoids have shown great potential to recapitulate the physiology of the human heart, they are unable to capture the complex crosstalk that takes place between the co-developing heart and endodermal organs, partly due to their distinct germ layer origins. In an effort to address this long-sought challenge, recent reports of multilineage organoids comprising both cardiac and endodermal derivatives have energized the efforts to understand how inter-organ, cross-lineage communications influence their respective morphogenesis. These co-differentiation systems have produced intriguing findings of shared signaling requirements for inducing cardiac specification together with primitive foregut, pulmonary, or intestinal lineages. Overall, these multilineage cardiac organoids offer an unprecedented window into human development that can reveal how the endoderm and heart cooperate to direct morphogenesis, patterning, and maturation. Further, through spatiotemporal reorganization, the co-emerged multilineage cells self-assemble into distinct compartments as seen in the cardiac-foregut, cardiac-intestine, and cardiopulmonary organoids and undergo cell migration and tissue reorganization to establish tissue boundaries. Looking into the future, these cardiac incorporated, multilineage organoids will inspire future strategies for improved cell sourcing for regenerative interventions and provide more effective models for disease investigation and drug testing. In this review, we will introduce the developmental context of coordinated heart and endoderm morphogenesis, discuss strategies for in vitro co-induction of cardiac and endodermal derivatives, and finally comment on the challenges and exciting new research directions enabled by this breakthrough.more » « less
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Recently, researchers have been attempting to control pluripotent stem cell fate or generate self-organized tissues from stem cells. Advances in bioengineering enable generation of organotypic structures, which capture the cellular components, spatial cell organization and even some functions of tissues or organs in development. However, only a few engineering tools have been utilized to regulate the formation and organization of spatially complex tissues derived from stem cells. Here, we provide a review of recent progress in the culture of organotypic structures in vitro , focusing on how microengineering approaches including geometric confinement, extracellular matrix (ECM) property modulation, spatially controlled biochemical factors, and external forces, can be utilized to generate organotypic structures. Moreover, we will discuss potential technologies that can be applied to further control both soluble and insoluble factors spatiotemporally in vitro . In summary, advanced engineered approaches have a great promise in generating miniaturized tissues and organs in a reproducible fashion, facilitating the cellular and molecular understanding of embryogenesis and morphogenesis processes.more » « less
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Mechanical forces provide critical biological signals to cells during healthy and aberrant organ development as well as during disease processes in adults. Within the cardiopulmonary system, mechanical forces, such as shear, compressive, and tensile forces, act across various length scales, and dysregulated forces are often a leading cause of disease initiation and progression such as in bronchopulmonary dysplasia and cardiomyopathies. Engineered in vitro models have supported studies of mechanical forces in a number of tissue and disease-specific contexts, thus enabling new mechanistic insights into cardiopulmonary development and disease. This review first provides fundamental examples where mechanical forces operate at multiple length scales to ensure precise lung and heart function. Next, we survey recent engineering platforms and tools that have provided new means to probe and modulate mechanical forces across in vitro and in vivo settings. Finally, the potential for interdisciplinary collaborations to inform novel therapeutic approaches for a number of cardiopulmonary diseases are discussed.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1063/5.0141269
