Astrocyte Mechanobiology: Linking Biomechanical Forces to Biochemical Signaling in the Central Nervous System

Astrocytes are the most abundant glial cells within the central nervous system. They are highly specialized mechanosensors able to detect the kinetics and magnitude of external biomechanical stimuli (i.e., matrix substrate stiffness and shear/compressive/tensile biomechanical strains). They integrate these biomechanical cues through a complex interplay of integrins, focal adhesions, junctional proteins and mechanosensitive channels. In development, this crosstalk secures astrocyte fate maturation and heterogeneity. However, in mechanically induced neural injuries, these mechanosensing elements can drive aberrant signaling. The range of astrocyte mechanoresponses in pathology include cytoskeletal remodeling that impacts cellular morphology and stiffness, disrupted calcium signaling, altered metabolism, pro-inflammatory signaling, and disruptive matrix remodeling. Ultimately, these mechanoresponses can form positive feedback loops that aggravate reactive astrogliosis, damage neural tissue, and altogether inhibit neural regeneration in these diseases. This review synthesizes the current knowledge of astrocyte mechanobiology during development and disease, and highlights the importance of continued investigation into the therapeutic potential of mitigating astrocyte mechanodysfunction in disease.