Mechanical and Functional Responses in Astrocytes under Alternating Deformation Modes Using Magneto‐Active Substrates

Abstract

This work introduces NeoMag, a system designed to enhance cell mechanics assays in substrate deformation studies. NeoMag uses multidomain magneto‐active materials to mechanically actuate the substrate, transmitting reversible mechanical cues to cells. The system boasts full flexibility in alternating loading substrate deformation modes, seamlessly adapting to both upright and inverted microscopes. The multidomain substrates facilitate mechanobiology assays on 2D and 3D cultures. The integration of the system with nanoindenters allows for precise evaluation of cellular mechanical properties under varying substrate deformation modes. The system was used to study the impact of substrate deformation on astrocytes, simulating mechanical conditions akin to traumatic brain injury and ischemic stroke. The results reveal local heterogeneous changes in astrocyte stiffness, influenced by the orientation of subcellular regions relative to substrate strain. These stiffness variations, exceeding 50% in stiffening and softening, and local deformations significantly alter calcium dynamics. Furthermore, sustained deformations induce actin network reorganisation and activate Piezo1 channels, leading to an initial increase followed by a long‐term inhibition of calcium events. Conversely, fast and dynamic deformations transiently activate Piezo1 channels and disrupt the actin network, causing long‐term cell softening. These findings unveil mechanical and functional alterations in astrocytes during substrate deformation, illustrating the multiple opportunities this technology offers.

Astrocyte regulation of extracellular space parameters across the sleep-wake cycle

“…Astrocytes, like other cells, respond to physical changes in the extracellular matrix (ECM) by converting structural changes of the parenchyma into intracellular signals through a process known as mechanotransduction ( Chen and Qiu, 2022 ; Donnaloja et al, 2023 ). Extreme mechanical stress may be exerted on parenchymal fluid routes in a variety of pathologies, like TBI ( Gomez-Cruz et al, 2024 ), and could potentially contribute to the reduced glymphatic transport observed in fluidopathies. Astrocyte endfeet are particularly sensitive to shear forces of ISF flux driven by vascular pulsatility, especially where the BBB is compromised and flow velocity is reduced ( Momin et al, 2021 ).…”