Mechanobiology of cells and cell systems, such as organoids

Abstract

Organoids are in vitro 3D self-organizing tissues that mimic embryogenesis. Organoid research is advancing at a tremendous pace, since it offers great opportunities for disease modeling, drug development and screening, personalized medicine, as well as understanding organogenesis. Mechanobiology of organoids is an unexplored area, which can shed light to several unexplained aspects of self-organization behavior in organogenesis. It is becoming evident that collective cell behavior is distinctly different from individual cells' conduct against certain stimulants. Inherently consisting of higher number of degrees of freedom for cell motility and more complex cell-to-cell and cell-to-extracellular matrix behavior, understanding mechanotransduction in organoids is even more challenging compared with cell communities in 2D culture conditions. Yet, deciphering mechanobiology of organoids can help us understand effects of mechanical cues in health and disease, and translate findings of basic research toward clinical diagnosis and therapy.

Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

“…Mechanical cues—Mechanical environmental cues like interstitial flow, flow-induced shear stress, and matrix stiffness directly affect cellular mechanobiology, i.e., the ability of the cells to sense mechanical stimuli and convert them in electrochemical and molecular processes [ 55 , 179 , 180 ]. As mechanical stimuli are particularly important in embryonic development as well as in tissue homeostasis, mechanical stress can lead to dysfunctional tissue/organ regulation.…”

“…Nonetheless, 2D culture systems, whether random, patterned, or multi-modular, lack the third dimension and the supportive microenvironment provided by the ECM typical of native biological tissues. This affects primarily cell polarization and morphology and, consequently, cell functions, as physical and mechanical constraints influence cell mechanotransduction, i.e., the activation of biochemical pathways upon external forces [ 55 ]. Given the high correlation between structure and function in body organs, the alterations occurring at the cellular and molecular levels are reflected at the organ level, for which 2D culture systems are known to miss key in vivo functional hallmarks of the organ of origin.…”

Advanced Spheroid, Tumouroid and 3D Bioprinted In-Vitro Models of Adult and Paediatric Glioblastoma

“…The location of GBM is a significant barrier to successful treatment. As well as making surgical resection difficult, the extracellular matrix (ECM) composition [ 23 , 24 ], tissue mechanics [ 15 , 25 ] and stromal-cell interactions [ 26 , 27 , 28 ] within the brain elicit unique tumour qualities. The brain provides tissue niches for stem-like cancer stem cells (CSC s ) and hypoxic regions develop, which further enables drug resistance and recurrence [ 29 , 30 ].…”

Biomedical applications of electrical stimulation

“…As a result, cell components will be dragged laterally. These mechanical signals alter the downstream gene expression and signaling pathways (i.e., mechanotransduction), causing change in various cellular processes, including cell mobility, cell proliferation, organogenesis, and development [77][78][79]. For example, mechanosensitive pathways such as Notch and Wnt/Ang2, play crucial roles in cardiovascular development and homeostasis in zebraish model [80].…”