Tissue mechanics regulate brain development, homeostasis and disease

Abstract

All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells – for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer.

Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels

“…The extracellular matrix (ECM) regulates cells in development, regeneration, and disease [1–3] through presentation of biochemical cues, and mechanical cues that alter the intrinsic and extrinsic forces generated by and imposed on cells, respectively [1]. Adherent cells respond to the resistance of the ECM to cellular traction forces, in a manner dependent on both the static mechanical properties of ECM, such as stiffness or modulus [4], and the time-dependent viscoelastic [5, 6] or plastic properties [7].…”

Brain Ventricular System and Cerebrospinal Fluid Development and Function: Light at the End of the Tube

“…Fluid pressure in brain ventricles can signal to neuroepithelial mechanosensors, and, when dysregulated though overproduction or disrupted drainage, can generate detrimental force on brain tissue. [14] CSF flow modulates function of the neuroepithelium through ion channels, but also helps distribute molecular signals and regulatory factors throughout the CNS. [14] The CSF contains metabolites, neurotransmitters, proteins, and extracellular vesicles that can function as molecular signals in the brain.…”

“…[14] CSF flow modulates function of the neuroepithelium through ion channels, but also helps distribute molecular signals and regulatory factors throughout the CNS. [14] The CSF contains metabolites, neurotransmitters, proteins, and extracellular vesicles that can function as molecular signals in the brain. [14] These can change gene expression and cellular function to support developmental and adult neural stem cells and their niches.…”

“…[14] The CSF contains metabolites, neurotransmitters, proteins, and extracellular vesicles that can function as molecular signals in the brain. [14] These can change gene expression and cellular function to support developmental and adult neural stem cells and their niches. We discuss the role of CSF in stem cell maintenance, and also in developmental signaling, neuronal differentiation, and brain health.…”

Changes in characteristics of periodontal ligament stem cells in spheroid culture

“…Recently, growing evidence has shown that the culture conditions in plastic culture plates are artificial and differ widely from those in vivo . For example, the hardness of the plastic culture dish is almost Giga‐Pascal order, and it is too hard compared to in vivo circumstances, such as 10 kPa for muscles and 0.4 kPa for lung and brain tissues . It has also been demonstrated that the hardness of the adherent surface affects the differentiation preferences of MSCs .…”