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Abstract The ability to adequately pump blood throughout the body is the result of tightly regulated feedback mechanisms that exist across many spatial scales in the heart. Diseases which impede the function at any one of the spatial scales can cause detrimental cardiac remodeling and eventual heart failure. An overarching goal of cardiac research is to use engineered heart tissue in vitro to study the physiology of diseased heart tissue, develop cell replacement therapies, and explore drug testing applications. A commonality within the field is to manipulate the flow of mechanical signals across the various spatial scales to direct self‐organization and build functional tissue. Doing so requires an understanding of how chemical, electrical, and mechanical cues can be used to alter the cellular microenvironment. We discuss how mathematical models have been used in conjunction with experimental techniques to explore various structure–function relations that exist across numerous spatial scales. We highlight how a systems biology approach can be employed to recapitulate in vivo characteristics in vitro at the tissue, cell, and subcellular scales. Specific focus is placed on the interplay between experimental and theoretical approaches. Various modeling methods are showcased to demonstrate the breadth and power afforded to the systems biology approach. An overview of modeling methodologies exemplifies how the strengths of different scientific disciplines can be used to supplement and/or inspire new avenues of experimental exploration. This article is categorized under:Models of Systems Properties and Processes > Mechanistic ModelsModels of Systems Properties and Processes > Cellular ModelsModels of Systems Properties and Processes > Organ, Tissue, and Physiological Models
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Lights up on organelles: Optogenetic tools to control subcellular structure and organization
Abstract Since the neurobiological inception of optogenetics, light‐controlled molecular perturbations have been applied in many scientific disciplines to both manipulate and observe cellular function. Proteins exhibiting light‐sensitive conformational changes provide researchers with avenues for spatiotemporal control over the cellular environment and serve as valuable alternatives to chemically inducible systems. Optogenetic approaches have been developed to target proteins to specific subcellular compartments, allowing for the manipulation of nuclear translocation and plasma membrane morphology. Additionally, these tools have been harnessed for molecular interrogation of organelle function, location, and dynamics. Optogenetic approaches offer novel ways to answer fundamental biological questions and to improve the efficiency of bioengineered cell factories by controlling the assembly of synthetic organelles. This review first provides a summary of available optogenetic systems with an emphasis on their organelle‐specific utility. It then explores the strategies employed for organelle targeting and concludes by discussing our perspective on the future of optogenetics to control subcellular structure and organization. This article is categorized under:Metabolic Diseases > Molecular and Cellular Physiology
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- Award ID(s):
- 1751840
- PAR ID:
- 10360593
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- WIREs Mechanisms of Disease
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2692-9368
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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