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Review
. 2020 Oct 1;7(4):40.
doi: 10.3390/jcdd7040040.

In Full Force. Mechanotransduction and Morphogenesis during Homeostasis and Tissue Regeneration

Vasiliki Tsata  1 , Dimitris Beis  1
Affiliations
Review

In Full Force. Mechanotransduction and Morphogenesis during Homeostasis and Tissue Regeneration

Vasiliki Tsata et al. J Cardiovasc Dev Dis. .

Abstract

The interactions of form and function have been the focus of numerous studies in the context of development and more recently regeneration. Our understanding on how cells, tissues and organs sense and interpret external cues, such as mechanical forces, is becoming deeper as novel techniques in imaging are applied and the relevant signaling pathways emerge. These cellular responses can be found from bacteria to all multicellular organisms such as plants and animals. In this review, we focus on hemodynamic flow and endothelial shear stress during cardiovascular development and regeneration, where the interactions of morphogenesis and proper function are more prominent. In addition, we address the recent literature on the role of extracellular matrix and fibrotic response during tissue repair and regeneration. Finally, we refer to examples where the integration of multi-disciplinary approaches to understand the biomechanics of cellular responses could be utilized in novel medical applications.

Keywords: biomechanics; cardiac valves; development; mechanotransduction; regeneration; tissue-engineering.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of key mechanotransduction stimuli and occurring cellular events from bacteria to humans.
Figure 2
Figure 2
Integration of external stimuli. The perception and interpretation of external signals starts at the cell membrane. Cells sense changes in their surface parameters through transmembrane receptors, ion or cell–cell junctional channels. Sensing of external cues originating from the extracellular matrix (ECM), takes place in specialized sites of interaction between the ECM and the membrane.
Figure 3
Figure 3
Signal propagation to the nucleus. Biochemical and mechanical stimuli are transferred to the nucleus and become effective through i) direct physical interactions of the membrane, the cytoskeleton and the nucleus and/or ii) the translocation of activated mediators from the cytoplasm to the nucleus. Eventually, stimuli surpassing a certain threshold can instruct transcriptional changes and regulate the gene expression pattern of a given cell.
Figure 4
Figure 4
Hemodynamics and stages of cardiogenesis in zebrafish and mammals. In both zebrafish and mammals, shear forces that occur from the oscillatory/retrograde blood flow and are driven by cardiac contractility and heart looping, direct valvulogenesis. Hence, cardiac valves are formed following the initiation of heart function. Valve cells originated from endocardial cells forming cardiac cushions. Valve Endothelial Cells (VECs) and Valve Intersitial Cells (VICs) can be identified in both systems. In zebrafish, embryonic cushions give rise to cardiac leaflets that invaginate and generate cardiac valves. In contrast, in mammals, endocardial cells undergo an endothelial-to-mesenchymal transition, delaminate generate cardiac valves upon invasion into the cardiac jelly. The outer layer of epicardial cells and the cardiac jelly is omitted in all schemes for figure clarity.
See this image and copyright information in PMC

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