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Emulating Biomechanical Environments in Microengineered Systems
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Jason Lee, Lei Mei, Daniel Chavarria, Aaron B. Baker
Overall, the inclusion of mechanical forces is key aspect of creating biomimetic systems that recapitulate normal physiologic function and disease processes. Chip-based systems have the advantage of creating multiple compartments to mimic structure. However, these systems can often be limited in creating higher throughput systems. Mesofluidic and well plate-based system for mechanobiology can be readily used for drug screening and high-throughput assays. They however have currently only been used to incorporate 2D culture systems. Thus, there remain opportunities for improvement on both types of assays to create biomimetic systems with 3D architecture than can be used to facilitate drug development and high-throughput science.
Centralized Endothelial Mechanobiology, Endothelial Dysfunction, and Atherosclerosis
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Ian Chandler Harding, Eno Essien Ebong
Mechanobiology is defined as the conversion of mechanical forces into physiological responses. Here, we are interested in mechanobiology that involves the conversion of shear stress into biochemical signal activation or inactivation within ECs. The endothelium possesses a multitude of endothelial mechanotransducers that assist in this process. We define a mechanotransducer as a biomolecule that can both sense and transduce mechanical forces into biochemical signals. There are many mechanotransducers that serve important roles in regulating endothelial function, such as the endothelial glycocalyx, cell-to-cell junctional proteins, focal adhesions, G proteins and G protein-coupled receptors, ion channels, primary cilia, and the endothelial cytoskeleton, among others that receive less attention (Figure 7.3) (Table 7.1) [35,36]. The majority of these are directly shear-sensitive cellular subcomponents that contain both intra- and extracellular regions. Such structures, like the endothelial glycocalyx and cilia, play a primary role in endothelial mechanobiology by directly sensing the shear stress that is transduced. This is known as centralized mechanotransduction. In contrast, structures that sense shear stress indirectly participate in mechanotransduction that is known as decentralized, not localized at the cell membrane [20]. Mechanosensors located at the cell membrane can play a pivotal role in decentralized mechanotransduction by activating mechanosensors further downstream. The cytoskeleton is an example of a decentralized mechanotransducer. In some scenarios, centralized and/or decentralized mechanotransduction fails, leading to the onset of vascular diseases [37–39].
Modeling and Analysis of the Cellular Mechanics Involved in the Pathophysiology of Disease/Injury
Published in Ning Xi, Mingjun Zhang, Guangyong Li, Modeling and Control for Micro/Nano Devices and Systems, 2017
Benjamin E. Reese, Scott C. Lenaghan, Mingjun Zhang
One of the most difficult aspects of model construction remains in the estimation of model parameters and the identification of the structural and regulatory behavior of biological networks. Generally, this is dependent on the understanding of the system being modeled and the availability of data that can be used to describe the system. Of particular interest to pathologists are changes in the mechanobiology of cells associated with disease. Mechanobiology focuses on how physical forces or changes in cell mechanics contribute to the development and physiology of cells and tissues. Structure–function relationships such as those involved in mechanobiology are known to regulate many biological processes, spanning multiple levels and length scales. As a result, numerous subcellular features, such as those involved in cytoskeletal rearrangement, influence the dynamic behavior of individual cells, which often affects surrounding cells through downstream signaling. This downstream signaling often serves as the origination signal of an injury or disease, and consequently, can be used for early detection of a pathological condition. Subtle modifications in the shape or structure of a cell could represent some of the earliest distinguishable factors indicating the onset of disease. For instance, mechanical forces applied to cells have been shown to regulate the progression of atherosclerosis and influence the transformation from a normal to malignant phenotype in certain cell types [1]. Not only can these external forces directly affect the mechanical response of cells, but they can also trigger the generation or suppression of biochemical and molecular signaling. Both the passive sensing and active modifications exhibited by different cell types due to these forces have an influence on the overall dynamics of cells and tissues. The ability to monitor and quantitatively measure these characteristic changes as a result of pathological events could facilitate earlier detection and provide further insight into healthy and diseased states.
Investigating orthodontic tooth movement: challenges and future directions
Published in Journal of the Royal Society of New Zealand, 2020
Fiona A. Firth, Rachel Farrar, Mauro Farella
Mechanobiology is an emerging branch of science associated with the response of cells to internal and external forces. Throughout the body, mechanical forces play important roles in regulatory processes such as protein synthesis, growth, differentiation and death (Wang and Thampatty 2006). Initially, when an orthodontic force is applied to a tooth, it moves within the socket, deforming the PDL on both surfaces non-uniformly. The PDL on the tension/apposition surface undergoes tensional deformation (positive strain), with the collagen fibres between the tooth and bone becoming stretched (Melsen 1999; Henneman et al. 2008). Conversely, the PDL on the compression/resorptive surface experiences compressive deformation (negative strain).